clozapine

Summary

Summary: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.

Top Publications

  1. pmc Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors
    Georgia M Alexander
    Department of Neurobiology, Duke University, Durham, NC 27710, USA
    Neuron 63:27-39. 2009
  2. pmc Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization
    Susan M Ferguson
    Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA
    Nat Neurosci 14:22-4. 2011
  3. pmc Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand
    Blaine N Armbruster
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 104:5163-8. 2007
  4. ncbi Antipsychotic-induced weight gain: a comprehensive research synthesis
    D B Allison
    Obesity Research Center, St Luke s Roosevelt Hospital, Columbia University College of Physicians and Surgeons, NY 10025, UDA
    Am J Psychiatry 156:1686-96. 1999
  5. ncbi Clozapine and the mitogen-activated protein kinase signal transduction pathway: implications for antipsychotic actions
    Jeff L Browning
    Department of Psychiatry, Scott and White Memorial Hospital, Central Texas Veterans Health Care System, and Texas A and M University System Health Science Center College of Medicine, Temple, Texas, USA
    Biol Psychiatry 57:617-23. 2005
  6. pmc Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation
    E Dong
    Psychiatric Institute, Department of Psychiatry, University of Illinois, 1601 West Taylor Street, Chicago, IL 60612, USA
    Proc Natl Acad Sci U S A 105:13614-9. 2008
  7. ncbi Clozapine and lithium require Caenorhabditis elegans β-arrestin and serum- and glucocorticoid-inducible kinase to affect Daf-16 (FOXO) localization
    Kathrine R Weeks
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana 71130 3932, USA
    J Neurosci Res 89:1658-65. 2011
  8. ncbi Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review
    David M Taylor
    Maudsley Hospital, London, United Kingdom
    J Clin Psychiatry 64:30-4. 2003
  9. ncbi A systematic review of the evidence of clozapine's anti-aggressive effects
    Catherine Frogley
    St Andrew s Academic Centre, Institute of Psychiatry, Northampton, UK
    Int J Neuropsychopharmacol 15:1351-71. 2012
  10. ncbi Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study
    D C Henderson
    Psychotic Disorders Program, Diabetes Clinical Research Center, Massachusetts General Hospital, Boston, USA
    Am J Psychiatry 157:975-81. 2000

Detail Information

Publications343 found, 100 shown here

  1. pmc Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors
    Georgia M Alexander
    Department of Neurobiology, Duke University, Durham, NC 27710, USA
    Neuron 63:27-39. 2009
    ..protein-coupled receptor (hM3Dq) selectively activated by the pharmacologically inert, orally bioavailable drug clozapine-N-oxide (CNO). Here, we expressed hM3Dq in forebrain principal neurons...
  2. pmc Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization
    Susan M Ferguson
    Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA
    Nat Neurosci 14:22-4. 2011
    ..of an engineered G protein-coupled receptor (hM(4)D), we found that activation of hM(4)D receptors with clozapine-N-oxide (CNO) potently reduced striatal neuron excitability...
  3. pmc Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand
    Blaine N Armbruster
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 104:5163-8. 2007
    ..receptors (GPCRs) that are activated solely by a pharmacologically inert drug-like and bioavailable compound (clozapine-N-oxide)...
  4. ncbi Antipsychotic-induced weight gain: a comprehensive research synthesis
    D B Allison
    Obesity Research Center, St Luke s Roosevelt Hospital, Columbia University College of Physicians and Surgeons, NY 10025, UDA
    Am J Psychiatry 156:1686-96. 1999
    ..The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight...
  5. ncbi Clozapine and the mitogen-activated protein kinase signal transduction pathway: implications for antipsychotic actions
    Jeff L Browning
    Department of Psychiatry, Scott and White Memorial Hospital, Central Texas Veterans Health Care System, and Texas A and M University System Health Science Center College of Medicine, Temple, Texas, USA
    Biol Psychiatry 57:617-23. 2005
    ..Here we show that the antipsychotic agent, clozapine, selectively activates the MEK/ERK MAPK pathway, and inhibition of this pathway reverses clozapine's actions in ..
  6. pmc Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation
    E Dong
    Psychiatric Institute, Department of Psychiatry, University of Illinois, 1601 West Taylor Street, Chicago, IL 60612, USA
    Proc Natl Acad Sci U S A 105:13614-9. 2008
    ..c. twice a day for 7 days) to hypermethylate promoters, including reelin and GAD67. Clinically relevant doses of clozapine (CLZ) (3.8 to 15 micromol/kg twice a day s.c. for 3 days) and sulpiride (SULP) (12...
  7. ncbi Clozapine and lithium require Caenorhabditis elegans β-arrestin and serum- and glucocorticoid-inducible kinase to affect Daf-16 (FOXO) localization
    Kathrine R Weeks
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana 71130 3932, USA
    J Neurosci Res 89:1658-65. 2011
    ..The most clinically effective antipsychotic drug is clozapine. With Caenorhabditis elegans as a model system, this study demonstrates that clozapine is unique among ..
  8. ncbi Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review
    David M Taylor
    Maudsley Hospital, London, United Kingdom
    J Clin Psychiatry 64:30-4. 2003
    b>Clozapine is indicated for the treatment of resistant schizophrenia, which is usually defined as failure to respond to adequate trials of 2 antipsychotics...
  9. ncbi A systematic review of the evidence of clozapine's anti-aggressive effects
    Catherine Frogley
    St Andrew s Academic Centre, Institute of Psychiatry, Northampton, UK
    Int J Neuropsychopharmacol 15:1351-71. 2012
    ..There is emerging evidence to suggest that the second-generation antipsychotic, clozapine, is effective at reducing this risk in patients with schizophrenia and some evidence to suggest that it may be ..
  10. ncbi Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study
    D C Henderson
    Psychotic Disorders Program, Diabetes Clinical Research Center, Massachusetts General Hospital, Boston, USA
    Am J Psychiatry 157:975-81. 2000
    The goal of this 5-year naturalistic study of patients treated with clozapine was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors, including weight gain, lipid abnormalities, age, clozapine ..
  11. ncbi Serum brain-derived neurotrophic factor and clozapine daily dose in patients with schizophrenia: a positive correlation
    Mariana Pedrini
    Bipolar Disorder Program, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
    Neurosci Lett 491:207-10. 2011
    ..b>Clozapine (CLZ) has been shown a beneficial effect on cognition in SZ in some studies and a detrimental effect in others...
  12. ncbi Clozapine induction of ERK1/2 cell signalling via the EGF receptor in mouse prefrontal cortex and striatum is distinct from other antipsychotic drugs
    Avril Pereira
    Department of Molecular Psychopharmacology, Mental Health Research Institute, Parkville, Victoria, Australia
    Int J Neuropsychopharmacol 15:1149-60. 2012
    ..Poor response to standard therapy leaves the APD clozapine as the only effective treatment for many patients...
  13. ncbi Metabolic syndrome with the atypical antipsychotics
    Pornpoj Pramyothin
    Boston Medical Center, Boston, Massachusetts 02118, USA
    Curr Opin Endocrinol Diabetes Obes 17:460-6. 2010
    ..This review aims to provide a summary of recent evidence on metabolic risks associated with SGAs, current recommendations for metabolic monitoring, and efficacy of treatment options currently available...
  14. ncbi Clozapine-induced ERK1 and ERK2 signaling in prefrontal cortex is mediated by the EGF receptor
    Avril Pereira
    Department of Molecular Psychopharmacology, Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, 3052, Victoria, Australia
    J Mol Neurosci 39:185-98. 2009
    The atypical antipsychotic drug clozapine is effective in treatment-refractory schizophrenia. The intracellular signaling pathways that mediate clozapine action remain unknown...
  15. ncbi D4 Dopamine receptor genes of zebrafish and effects of the antipsychotic clozapine on larval swimming behaviour
    W Boehmler
    Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA
    Genes Brain Behav 6:155-66. 2007
    ..of zebrafish D4 dopamine receptors (D4Rs) and the response of larval zebrafish to the atypical antipsychotic clozapine. The D4R is of interest because of its high affinity for clozapine, while interest in clozapine stems from its ..
  16. ncbi Polymorphisms of the LEP- and LEPR genes, metabolic profile after prolonged clozapine administration and response to the antidiabetic metformin
    Erika Fernandez
    Institute of Clinical Research Dr Américo Negrette, Zulia University Medical School, Maracaibo, Venezuela
    Schizophr Res 121:213-7. 2010
    ..was explored by assessing the anthropometric and metabolic profile and the response to metformin (MET) of clozapine- (CLZ) treated schizophrenia patients according to their single nucleotide polymorphisms (SNPs) in the leptin ..
  17. pmc Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation
    Johan Fernø
    Dr Einar Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, Norway
    PLoS ONE 6:e20571. 2011
    ..to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear...
  18. ncbi Clozapine administration in adolescence prevents postpubertal emergence of brain structural pathology in an animal model of schizophrenia
    Yael Piontkewitz
    Department of Psychology, Tel Aviv University, Israel
    Biol Psychiatry 66:1038-46. 2009
    ..We used a neurodevelopmental animal model of schizophrenia to assess the efficacy of the atypical antipsychotic clozapine to prevent neuroanatomical deterioration.
  19. pmc Clozapine impairs insulin action by up-regulating Akt phosphorylation and Ped/Pea-15 protein abundance
    Fabio Panariello
    Dipartimento di Neuroscienze, Sezione di Psichiatria, Laboratorio di Psichiatria Molecolare, University of Napoli Federico II, Napoli, Italy
    J Cell Physiol 227:1485-92. 2012
    ..We investigated whether clozapine may directly affect insulin action by analyzing insulin signaling in vitro and in vivo...
  20. ncbi Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine
    H H Van Tol
    Department of Pharmacology, University of Toronto, Ontario, Canada
    Nature 350:610-4. 1991
    ..In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine is one of the most favoured antipsychotics because it does not cause tardive dyskinesia...
  21. ncbi The effects of clozapine and risperidone on spatial working memory in schizophrenia
    Susan R McGurk
    Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L Levy Pl, New York, NY 10029, USA
    Am J Psychiatry 162:1013-6. 2005
    The purpose of this investigation was to evaluate the effects of clozapine and risperidone on spatial working memory in patients with schizophrenia.
  22. ncbi Interaction of mGlu2/3 agonism with clozapine and lurasidone to restore novel object recognition in subchronic phencyclidine-treated rats
    Masakuni Horiguchi
    Division of Psychopharmacology, Vanderbilt University Medical Center, Nashville, TN 37212, USA
    Psychopharmacology (Berl) 217:13-24. 2011
    ..Atypical antipsychotic drugs (APDs) reverse the effects of subchronic PCP on NOR. The effect of metabotropic glutamate₂/₃ receptor (mGlu₂/₃) agonists upon NOR is unknown...
  23. ncbi Phospholipase C-beta1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration
    C E McOmish
    Howard Florey Institute, University of Melbourne, Melbourne, Vic, Australia
    Mol Psychiatry 13:661-72. 2008
    ..Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit ..
  24. pmc Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs
    Miguel Fribourg
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cell 147:1011-23. 2011
    Atypical antipsychotic drugs, such as clozapine and risperidone, have a high affinity for the serotonin 5-HT(2A) G protein-coupled receptor (GPCR), the 2AR, which signals via a G(q) heterotrimeric G protein...
  25. pmc Exploring off-targets and off-systems for adverse drug reactions via chemical-protein interactome--clozapine-induced agranulocytosis as a case study
    Lun Yang
    Bio X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education, Shanghai Jiao Tong University, Shanghai, China
    PLoS Comput Biol 7:e1002016. 2011
    ..b>Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening ..
  26. ncbi Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus
    Nader D Halim
    Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, NIH, Bethesda, MD 20892 1385, USA
    Neuropsychopharmacology 29:1063-9. 2004
    ..Haloperidol (0.05 and 2 mg/kg), clozapine (0.5 and 20 mg/kg), or vehicle were administered i.p...
  27. ncbi Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT)
    Herbert Y Meltzer
    Psychiatric Hospital at Vanderbilt, 1601 23rd Ave S, Suite 306, Nashville, TN 37212, USA
    Arch Gen Psychiatry 60:82-91. 2003
    Approximately 50% of patients with schizophrenia or schizoaffective disorder attempt suicide, and approximately 10% die of suicide. Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients.
  28. pmc Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents
    Vance L Albaugh
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    Obesity (Silver Spring) 14:36-51. 2006
    ..To characterize a model of atypical antipsychotic drug-induced obesity and evaluate its mechanism...
  29. ncbi Haloperidol and clozapine decrease S100B release from glial cells
    J Steiner
    Department of Psychiatry, University of Magdeburg, Germany
    Neuroscience 167:1025-31. 2010
    ..In this study, we explored the effects of the typical antipsychotic haloperidol and the atypical prototype drug clozapine on the release of S100B by astrocytic C6 cells and oligodendrocytic OLN-93 cells...
  30. ncbi Treatment pathway and patterns of clozapine prescribing for schizophrenia in New Zealand
    Amanda J Wheeler
    Clinical Research and Resource Centre, Waitemata District Health Board, Auckland, New Zealand
    Ann Pharmacother 42:852-60. 2008
    To describe the treatment pathway and patterns of clozapine use in patients with schizophrenia, including coprescribed psychotropic medications, and compare the extent of coprescribing of clozapine with that of non-clozapine ..
  31. ncbi Clozapine improves deficient inhibitory auditory processing in DBA/2 mice, via a nicotinic cholinergic mechanism
    Johanna K Simosky
    Department of Pharmacology, University of Colorado Health Sciences Center, Campus Box C268 71, 4200 East 9th Avenue, Denver, CO 80262, USA
    Psychopharmacology (Berl) 165:386-96. 2003
    ..The atypical antipsychotic clozapine also normalizes this deficit in schizophrenia patients, but by an unknown mechanism.
  32. ncbi The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update
    Troy A Moore
    Department of Psychiatry, The University of Texas Health Science Center at San Antonio, USA
    J Clin Psychiatry 68:1751-62. 2007
    ....
  33. ncbi Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs
    Frank M Theisen
    Clinical Research Group, Department of Child and Adolescent Psychiatry, University of Marburg, Hans Sachs Str 6, D 35039 Marburg, Germany
    Psychiatr Genet 15:285-9. 2005
    ..in antipsychotic-induced weight gain, we explored the similarity in body mass index (BMI) (kg/m(2)) change under clozapine only (clozapine DeltaBMI) and upon additional inclusion of BMI change under prior antipsychotic medication (..
  34. ncbi Increased cortical inhibition in persons with schizophrenia treated with clozapine
    Zafiris J Daskalakis
    Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
    J Psychopharmacol 22:203-9. 2008
    ..The purpose of this study, therefore, was to examine the effects of clozapine on TMS measures of CI and to compare these effects to unmedicated persons with schizophrenia and healthy ..
  35. ncbi Haloperidol- and clozapine-induced oxidative stress in the rat brain
    Manuela Polydoro
    Centro de Estudos em Estresse Oxidativo, Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, 90035 003 Porto Alegre, RS, Brazil
    Pharmacol Biochem Behav 78:751-6. 2004
    ..Adult male Wistar rats received daily injections of HAL (1.5 mg/kg) or clozapine (CLO, 25 mg/kg), an atypical neuroleptic, for 28 days. Control animals were given saline (SAL; NaCl 0.9%)...
  36. ncbi Increased serum S100B in elderly, chronic schizophrenic patients: negative correlation with deficit symptoms
    Andrea Schmitt
    Central Institute of Mental Health, P O Box 12 21 20, D 68072 Mannheim, Germany
    Schizophr Res 80:305-13. 2005
    ..assessed detailed psychopathology and neuropsychological performance and determined serum levels of haloperidol, clozapine and its two main metabolites desmethylclozapine and clozapine metabolite N-oxid by HPLC...
  37. ncbi Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol
    Jan Volavka
    Nathan Kline Institute, Orangeburg, NY 10982, USA
    J Clin Psychiatry 65:57-61. 2004
    ....
  38. ncbi alpha2C-Adrenoceptor blockade by clozapine and other antipsychotic drugs
    Hans O Kalkman
    Novartis Pharma AG, Research Nervous System, Building WSJ 360 405, CH 4002 Basel, Switzerland
    Eur J Pharmacol 462:33-40. 2003
    ..Therefore, the antagonistic potencies of the antipsychotics clozapine, chlorpromazine, risperidone, olanzapine, haloperidol, quetiapine, ziprasidone, iloperidone and aripiprazole ..
  39. ncbi Factors affecting interindividual differences in clozapine response: a review and case report
    Francesco Saverio Bersani
    Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
    Hum Psychopharmacol 26:177-87. 2011
    b>Clozapine is the most powerful new‐generation antipsychotic. Although this drug leads to great therapeutic benefits, two types of undesirable conditions frequently occur with its use: side effects and resistance to treatment...
  40. ncbi Current use of clozapine in Parkinson disease and related disorders
    Alissa A Thomas
    Alpert Medical School, Brown University, Providence, RI 02886, USA
    Clin Neuropharmacol 33:14-6. 2010
    b>Clozapine has been shown to be effective in the treatment of Parkinson disease psychosis and tremor; however, use of clozapine has been limited because of potential adverse effects and stringent monitoring criteria.
  41. ncbi Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study
    F Durif
    Department of Neurology, Hopital Gabriel Montpied, Clermont Ferrand, France
    Neurology 62:381-8. 2004
    To investigate the efficacy and safety of clozapine in the treatment of levodopa-induced dyskinesias (LID) in patients with severe Parkinson disease (PD).
  42. ncbi Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant
    R Hwang
    Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
    Pharmacogenomics J 10:200-18. 2010
    ..However, treatment refractoriness, in spite of complete D2 blockade, as well as the efficacy of clozapine (CLZ) in a portion of this patient population, indicates the involvement of other factors as well...
  43. ncbi Hepatitis C in schizophrenia: screening experience in a community-dwelling clozapine cohort
    Oliver Freudenreich
    Massachusetts General Hospital Schizophrenia Program, Freedom Trail Clinic, the Division of Infectious Diseases and Partners AIDS Research Center, and Harvard Medical School, Boston, MA 02114, USA
    Psychosomatics 48:405-11. 2007
    ..of hepatitis C in a diagnostically well-defined sample, the authors screened all schizophrenia outpatients in a clozapine clinic (N=98) for HCV antibodies...
  44. ncbi Berberine inhibits SREBP-1-related clozapine and risperidone induced adipogenesis in 3T3-L1 cells
    Yueshan Hu
    Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA
    Phytother Res 24:1831-8. 2010
    ..and potentially serious complication associated with the treatment of second generation antipsychotics such as clozapine and risperidone...
  45. ncbi Clozapine-associated diabetes
    E Koller
    Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857, USA
    Am J Med 111:716-23. 2001
    b>Clozapine is a potent antipsychotic agent that has been marketed since 1990. Several published reports of diabetes mellitus occurring with clozapine therapy have appeared during the past 5 years...
  46. ncbi Association study of 27 annotated genes for clozapine pharmacogenetics: validation of preexisting studies and identification of a new candidate gene, ABCB1, for treatment response
    Seung Tae Lee
    Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    J Clin Psychopharmacol 32:441-8. 2012
    Pharmacogenetic studies on clozapine (CLZ) have provided meaningful insights but have shown redundancies owing to wide interindividual variability and insufficient replication...
  47. ncbi Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study
    Emilio Sacchetti
    Brescia University School of Medicine, Brescia, Italy
    Schizophr Res 110:80-9. 2009
    ..18-week, randomized, flexible-dose, double-blind, double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients...
  48. ncbi Metabolic effects of adjunctive aripiprazole in clozapine-treated patients with schizophrenia
    X Fan
    Schizophrenia Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
    Acta Psychiatr Scand 127:217-26. 2013
    This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine-treated patients with schizophrenia.
  49. ncbi The relationship of clozapine and haloperidol treatment response to prefrontal, hippocampal, and caudate brain volumes
    Celso Arango
    Maryland Psychiatric Research Center, Department of Psychariatry, University of Maryland, MD 21228, USA
    Am J Psychiatry 160:1421-7. 2003
    The study was designed to assess the predictive relationship between brain structure volume and positive and negative symptom response to clozapine and haloperidol.
  50. ncbi Clozapine serum concentrations are lower in smoking than in non-smoking schizophrenic patients
    N H Seppälä
    Department of Clinical Psychiatry, Tampere University Hospital, Finland
    Pharmacol Toxicol 85:244-6. 1999
    Serum concentrations of clozapine and its main metabolite demethylclozapine were measured in 44 schizophrenic inpatients, of whom ten were non-smokers and 34 smokers...
  51. ncbi Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in schizophrenia: a study of patients treated with haloperidol or clozapine
    Clarissa Severino Gama
    Departamento de Psiquiatria, Hospital de Clínicas de Porto Alegre HCPA, Laboratório de Psiquiatria Experimental Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul UFRGS, Porto Alegre, Brazil
    Prog Neuropsychopharmacol Biol Psychiatry 30:512-5. 2006
    ..SOD and TBARS in two groups of chronic medicated DSM-IV schizophrenic patients, under haloperidol (n = 10) or clozapine (n = 7) and a group of healthy controls (n = 15). Serum SOD and TBARS were significantly higher (p = 0...
  52. ncbi Weight gain with clozapine: 8-year cohort naturalistic study among hospitalized Chinese schizophrenia patients
    Ya Mei Bai
    Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
    Schizophr Res 108:122-6. 2009
    b>Clozapine is associated with significant weight gain. However, it is still debatable whether the majority of weight gain occurs in the early phase of treatment or if weight gain is a persistent side effect...
  53. ncbi Clozapine: balancing safety with superior antipsychotic efficacy
    Herbert Y Meltzer
    Northwestern Feinberg School of Medicine, Ward Building 12 104, 303 East Chicago Avenue, Chicago, IL 60611, USA
    Clin Schizophr Relat Psychoses 6:134-44. 2012
    b>Clozapine is often referred to as the gold standard for the treatment of schizophrenia and yet has also been described as the most underutilized treatment for schizophrenia supported by solid evidence-based medicine...
  54. pmc Homocysteine levels in patients with schizophrenia on clozapine monotherapy
    Adam Wysokiński
    Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Czechosłowacka 8 10, 92 216, Łódź, Poland
    Neurochem Res 38:2056-62. 2013
    We tested the hypothesis that homocysteine levels are higher in blood of schizophrenic subjects on clozapine monotherapy than in healthy controls and they correlate with anthropometric measurements, laboratory tests and results of ..
  55. ncbi Clozapine resistance: augmentation strategies
    Stefano Porcelli
    Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy
    Eur Neuropsychopharmacol 22:165-82. 2012
    b>Clozapine (CLZ) is not effective in more than 50% of treatment-resistant schizophrenic patients...
  56. ncbi Psychiatrists' attitude towards and knowledge of clozapine treatment
    J Nielsen
    Unit for Psychiatric Research, Aalborg Psychiatric Hospital, 9100 Aalborg, Denmark
    J Psychopharmacol 24:965-71. 2010
    b>Clozapine is, in most countries, underutilized and the initiation of clozapine is often delayed. The purpose of this study is to investigate the reasons for the delay and the underutilization of clozapine...
  57. ncbi Homocysteine levels and glucose metabolism in non-obese, non-diabetic chronic schizophrenia
    D C Henderson
    Schizophrenia Program, Massachusetts General Hospital, Boston, MA, USA
    Acta Psychiatr Scand 113:121-5. 2006
    ..We studied a sample of schizophrenia out-patients to test the hypotheses that serum homocysteine concentrations would correlate positively with measures of glucose metabolism...
  58. ncbi Adjunct divalproex or lithium to clozapine in treatment-resistant schizophrenia
    Deanna L Kelly
    Maryland Psychiatric Research Center, University of Maryland, Box 21247, Baltimore, MD 21228, USA
    Psychiatr Q 77:81-95. 2006
    ..examined adjunct divalproex (N = 15) or lithium (N = 9) in treatment-resistant schizophrenia patients added to clozapine and compared to clozapine monotherapy (N = 25)...
  59. ncbi Effect of clozapine, haloperidol, or M100907 on phencyclidine-activated glutamate efflux in the prefrontal cortex
    B W Adams
    Department of Psychiatry, Yale University School of Medicine, Veterans Administration Medical Center, West Haven, Connecticut 06516, USA
    Biol Psychiatry 50:750-7. 2001
    ..Here, we examined whether antipsychotic drugs influence this increase. METHODS: The effect of haloperidol, clozapine or the 5-HT(2A) antagonist, M100907, on PCP-induced increase in cortical glutamate efflux was examined by ..
  60. ncbi The effect of smoking and cytochrome P450 CYP1A2 genetic polymorphism on clozapine clearance and dose requirement
    Jan van der Weide
    Department of Clinical Chemistry, St Jansdal Hospital, Harderwijk, The Netherlands
    Pharmacogenetics 13:169-72. 2003
    b>Clozapine is an atypical antipsychotic drug that is metabolized to a major extent by the cytochrome P450 enzyme CYP1A2...
  61. pmc Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia
    Shon W Lewis
    University of Manchester, London
    Schizophr Bull 32:715-23. 2006
    There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs...
  62. ncbi Increased serum S100B levels in chronic schizophrenic patients on long-term clozapine or typical antipsychotics
    Ling Yan Qi
    Center for Biological Psychiatry, Beijing Huilongguan Hospital, Beijing, PR China
    Neurosci Lett 462:113-7. 2009
    ..To examine the potentially differential effect of clozapine compared to typical antipsychotics on serum S100B and the relationship between S100B levels and psychopathology ..
  63. pmc Antipsychotic drugs activate the C. elegans akt pathway via the DAF-2 insulin/IGF-1 receptor
    Kathrine R Weeks
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana, USA
    ACS Chem Neurosci 1:463-73. 2010
    ..Because untreated schizophrenics have been reported to have low levels of Akt signaling, increased Akt signaling might contribute to the therapeutic actions of antipsychotic drugs...
  64. ncbi Effect of aripiprazole augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study
    Maria Rosaria A Muscatello
    Section of Psychiatry, Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, University of Messina, Messina, Italy
    Schizophr Res 127:93-9. 2011
    ..in combination is a common treatment strategy for those patients who have demonstrated a suboptimal response to clozapine; nevertheless, evidence suggesting potential advantages of combination treatment with clozapine plus one ..
  65. ncbi Nicotine and clozapine selectively reverse a PCP-induced deficit of PPI in BALB/cByJ but not NMRI mice: comparison with risperidone
    J T Andreasen
    Neurosearch A S, 93 Pederstrupvej, Ballerup, DK 2750, Denmark
    Behav Brain Res 167:118-27. 2006
    ..g. alpha(7) receptors, is plausible. Clozapine, but not risperidone, also only reversed the PCP deficit of PPI in BALB/cByJ...
  66. ncbi Pharmacotherapy for treatment-refractory schizophrenia
    Scott P Van Sant
    Medical College of Georgia, Department of Psychiatry and Health Behavior, Augusta, GA 30912, USA
    Expert Opin Pharmacother 12:411-34. 2011
    ....
  67. ncbi Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial
    W Wolfgang Fleischhacker
    Biological Psychiatry Division, Medical University Innsbruck, Innsbruck, Austria
    Int J Neuropsychopharmacol 13:1115-25. 2010
    b>Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk...
  68. ncbi Relationship between levels of insulin or triglycerides and serum concentrations of the atypical antipsychotics clozapine and olanzapine in patients on treatment with therapeutic doses
    K I Melkersson
    Department of Molecular Medicine, Sollentuna Psychiatric Polyclinic, Karolinska Institute, Stockholm, Sweden
    Psychopharmacology (Berl) 170:157-66. 2003
    Recent results suggest that treatment with the atypical antipsychotics clozapine and olanzapine is associated with increased insulin and lipid levels.
  69. ncbi Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study
    Chih Sung Liang
    Department of Psychiatry, Beitou Armed Forces Hospital, 60 Shin Ming Road, Beitou, Taipei, Taiwan
    Schizophr Res 119:138-44. 2010
    b>Clozapine-induced sialorrhea (CIS) is a subjective distressing adverse effect and occurs in 31%-57% of schizophrenic patients receiving clozapine therapy...
  70. ncbi A parametric study of the acute effects of antipsychotic drugs on glucose sensitivity in an animal model
    Heidi N Boyda
    Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
    Prog Neuropsychopharmacol Biol Psychiatry 34:945-54. 2010
    ..The effects of administration of clozapine (2mg/kg; 20mg/kg), olanzapine (1.5mg/kg; 15 mg/kg), risperidone (0.5mg/kg; 2.5mg/kg) and haloperidol (0...
  71. ncbi Topiramate augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study
    M R A Muscatello
    Section of Psychiatry, Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, University of Messina, Italy
    J Psychopharmacol 25:667-74. 2011
    ..symptomatology and cognitive functioning in a sample of treatment-resistant schizophrenic patients receiving clozapine. After clinical and cognitive assessments were randomly allocated to receive either up to 200 mg/day of ..
  72. ncbi Effect of antipsychotics on succinate dehydrogenase and cytochrome oxidase activities in rat brain
    Emilio L Streck
    Laboratório de Fisiopatologia Experimental, Programa de Pos Graduacao em Ciencias da Saude, Universidade do Extremo Sul Catarinense, 88806 000 Criciuma, SC, Brazil
    Naunyn Schmiedebergs Arch Pharmacol 376:127-33. 2007
    ..of mitochondria, in this work, we evaluated the activities of these enzymes in rat brain after haloperidol, clozapine, olanzapine, or aripiprazole chronic administration...
  73. ncbi Selective modulation of fibroblast growth factor-2 expression in the rat brain by the atypical antipsychotic clozapine
    M A Riva
    Center for Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Italy
    Neuropharmacology 38:1075-82. 1999
    ..rat brain, the expression of basic fibroblast growth factor (FGF-2) in response to the atypical antipsychotic clozapine. We found that acute or chronic administration of this compound produced a selective increase of FGF-2 mRNA and ..
  74. ncbi Agonist activity of N-desmethylclozapine at delta-opioid receptors of human frontal cortex
    Maria C Olianas
    Department of Neuroscience, Section of Biochemical Pharmacology, University of Cagliari, 09042 Monserrato, CA, Italy
    Eur J Pharmacol 607:96-101. 2009
    The clozapine metabolite N-desmethylclozapine (NDMC) has been recently shown to act at different neurotransmitter receptors and to display both antagonist and agonist activities...
  75. ncbi Clozapine treatment causes oxidation of proteins involved in energy metabolism in lymphoblastoid cells: a possible mechanism for antipsychotic-induced metabolic alterations
    Muhammad R Baig
    Department of Psychiatry, The University of Texas Health Science Center, San Antonio, Texas 78229, USA
    J Psychiatr Pract 16:325-33. 2010
    ..Int J Neuropsychopharmacol 2008;11:1097-104), using a novel proteomic approach, we showed that clozapine treatment in SKNSH cells induces oxidation of proteins involved in energy metabolism, leading us to hypothesize ..
  76. ncbi Extended release metformin for metabolic control assistance during prolonged clozapine administration: a 14 week, double-blind, parallel group, placebo-controlled study
    Edgardo Carrizo
    Institute of Clinical Research Dr Américo Negrette, Zulia University Medical School, Maracaibo, Venezuela
    Schizophr Res 113:19-26. 2009
    b>Clozapine is the most effective agent in treatment-resistant schizophrenia. However, it is frequently associated with excessive body weight (BW) gain, type 2 diabetes mellitus and hyperlipidemia...
  77. ncbi Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis
    Urs Meyer
    Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology ETH Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland
    Psychopharmacology (Berl) 208:531-43. 2010
    ..Converging evidence indicates that prenatal exposure to immune challenge can induce long-term cognitive deficits relevant to schizophrenia. Such cognitive impairments may be related to deficient hippocampal neurogenesis at adult age...
  78. ncbi Clozapine-, but not haloperidol-, induced increases in deltaFosB-like immunoreactivity are completely blocked in the striatum of mice lacking D3 dopamine receptors
    George S Robertson
    Department of Psychiatry, Sir Charles Tupper Medical Building, 5850 College Street, Halifax, Nova Scotia B3H 1X5, Canada
    Eur J Neurosci 20:3189-94. 2004
    ..and pharmacological evidence, we have proposed that D3 receptor antagonism plays a role in the mediation of clozapine-, but not haloperidol-, induced immediate-early gene expression in the striatum...
  79. ncbi Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum: candidate mechanism for superior efficacy?
    Christine E Marx
    Duke University Medical Center, Durham NC, USA
    Pharmacol Biochem Behav 84:598-608. 2006
    b>Clozapine demonstrates superior efficacy in patients with schizophrenia, but the precise mechanisms contributing to this clinical advantage are not clear...
  80. ncbi Clinical correlates of clozapine prescription for schizophrenia in China
    Yu Tao Xiang
    Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China
    Hum Psychopharmacol 22:17-25. 2007
    Few studies have investigated the prescription patterns of clozapine in outpatients with schizophrenia in China. It is an important issue due to clozapine's high efficacy and potentially fatal side effect profile...
  81. pmc Atypical antipsychotics clozapine and quetiapine attenuate prepulse inhibition deficits in dopamine transporter knockout mice
    Susan B Powell
    aDepartment of Psychiatry, University of California, San Diego, La Jolla, California 92093 0804, USA
    Behav Pharmacol 19:562-5. 2008
    ..Here we report that treatment with clozapine (3 mg/kg) or quetiapine (2.5 mg/kg) attenuated prepulse inhibition deficits in male DAT knockout mice...
  82. pmc Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT(1A) Receptor-Dependent Mechanism
    Lucila Kargieman
    Department of Neurochemistry and Neuropharmacology, Institut d Investigacions Biomediques de Barcelona, Consejo Superior de Investigaciones Científicas IIBB CSIC, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, Barcelona, Spain
    Neuropsychopharmacology 37:723-33. 2012
    ..15-4 Hz) in rat PFC. Both effects were reversed by classical (haloperidol) and atypical (clozapine) antipsychotic drugs...
  83. ncbi Augmentation of clozapine with a second antipsychotic - a meta-analysis
    D M Taylor
    Pharmacy Department, Maudsley Hospital, London, UK
    Acta Psychiatr Scand 125:15-24. 2012
    To examine using meta-analysis the effect of adding a second antipsychotic to established clozapine monotherapy.
  84. ncbi Do clozapine and risperidone affect social competence and problem solving?
    Alan S Bellack
    Mental Health Research, Education and Clinical Center, VA Maryland Health Care System, Baltimore 21201, USA
    Am J Psychiatry 161:364-7. 2004
    The purpose of this investigation was to evaluate the effects of clozapine and risperidone on social skill and problem solving in patients with schizophrenia.
  85. ncbi Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: association with N-methyl-D-aspartic acid receptor up-regulation
    Laura Gray
    Howard Florey Institute, University of Melbourne, Victoria, Australia
    Int J Neuropsychopharmacol 12:45-60. 2009
    ..Chronic administration of the antipsychotic drug clozapine ameliorated the locomotor disruption and reversed the PPI deficit, but did not improve Y-maze performance...
  86. ncbi N-desmethylclozapine (NDMC) is an antagonist at the human native muscarinic M(1) receptor
    David R Thomas
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, Harlow, Essex CM19 5AW UK
    Neuropharmacology 58:1206-14. 2010
    ..the human recombinant and rat native M(1) mAChR, a property suggested to contribute to the clinical efficacy of clozapine. However, the profile of action of NDMC at the human native M(1) mAChR has not been reported...
  87. ncbi Optimizing clozapine treatment
    J Nielsen
    Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital, Denmark
    Acta Psychiatr Scand 123:411-22. 2011
    b>Clozapine treatment remains the gold standard for treatment-resistant schizophrenia, but treatment with clozapine is associated with several side-effects that complicate the use of the drug...
  88. ncbi Clozapine-induced obsessive-compulsive syndromes improve in combination with aripiprazole
    Susanne Englisch
    Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany
    Clin Neuropharmacol 32:227-9. 2009
    ..subgroup developed secondary OCS during treatment with antiserotonergic, atypical antipsychotic agents such as clozapine. Although cognitive behavioral therapy and antiobsessive antidepressants brought up inconsistent results, in ..
  89. ncbi Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial
    Corrado Barbui
    World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Organization, Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Verona, Italy
    J Clin Psychopharmacol 31:266-73. 2011
    This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not ..
  90. ncbi The combined use of risperidone long-acting injection and clozapine in patients with schizophrenia non-adherent to clozapine: a case series
    - Se Hyun Kim
    Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul 110 744, Republic of Korea
    J Psychopharmacol 24:981-6. 2010
    Poor adherence to clozapine treatment represents an important problem in clinical practice because additional useful treatment options are unavailable...
  91. pmc Haloperidol and clozapine differentially affect the expression of arrestins, receptor kinases, and extracellular signal-regulated kinase activation
    Mohamed Rafiuddin Ahmed
    Department of Pharmacology, Vanderbilt University Medical Center, Preston Research Building, Room 422, Nashville, TN 37232, USA
    J Pharmacol Exp Ther 325:276-83. 2008
    ..p.) or clozapine (20 mg/kg i.p.) 2 or 24 h after the last injection in 11 brain regions...
  92. pmc Upregulation of NRG-1 and VAMP-1 in human brain aggregates exposed to clozapine
    Gursharan Chana
    Department of Psychiatry, University of California San Diego, La Jolla, CA 92093 0603, USA
    Schizophr Res 113:273-6. 2009
    ..In relation to a potential therapeutic mechanism for atypical antipsychotic medications, clozapine has been shown to increase both NRG-1 levels and synaptic markers in rodents...
  93. ncbi Schizophrenic patients treated with clozapine or olanzapine perform better on theory of mind tasks than those treated with risperidone or typical antipsychotic medications
    Ioulia Savina
    Department of Psychology, Queen s University, Kingston ON, Canada, K7L 3N6
    Schizophr Res 94:128-38. 2007
    ..Olanzapine or clozapine but not typical antipsychotics or risperidone preferentially affect c-fos expression in mPFC in animals...
  94. ncbi Evaluation of the role of P-glycoprotein in the uptake of paroxetine, clozapine, phenytoin and carbamazapine by bovine retinal endothelial cells
    Lynn W Maines
    Department of Pharmacology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    Neuropharmacology 49:610-7. 2005
    ..neither verapamil nor PGP-4008 affected the intracellular accumulation of [3H]paroxetine, [14C]phenytoin, [3H]clozapine or [14C]carbamazapine, indicating that these drugs are not substrates for Pgp...
  95. ncbi Effects of clozapine and olanzapine on cytokine systems are closely linked to weight gain and drug-induced fever
    Michael Kluge
    Max Planck Institute of Psychiatry, Munich, Germany
    Psychoneuroendocrinology 34:118-28. 2009
    The second generation antipsychotics clozapine and olanzapine are known to cause weight gain. However, only clozapine is associated with drug-induced fever...
  96. ncbi Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine
    Jeffrey A Lieberman
    Department of Psychiatry, CB 7160, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7160, USA
    Neuropsychopharmacology 28:995-1003. 2003
    ..examined efficacy and safety in a randomized, double-blind, 52-week trial, comparing chlorpromazine (CPZ) and clozapine (CLZ) in treatment naive patients experiencing their first episode of schizophrenia...
  97. ncbi Noradrenaline transporter blockers raise extracellular dopamine in medial prefrontal but not parietal and occipital cortex: differences with mianserin and clozapine
    V Valentini
    Department of Toxicology and Centre of Excellence Neurobiology of Addiction, University of Cagliari, Cagliari, Italy
    J Neurochem 88:917-27. 2004
    ..and desipramine, two NA transporter blockers, of mianserin, an antagonist of alpha2 and 5-HT2 receptors, and of clozapine, an atypical antipsychotic, on dialysate DA in the medial PFCX, ParCX and OccCX was studied...
  98. ncbi The atypical antipsychotic drug clozapine enhances chronic PCP-induced regulation of prefrontal cortex 5-HT2A receptors
    Lucinda J Steward
    Yoshitomi Research Institute of Neuroscience in Glasgow YRING, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK
    Neuropharmacology 47:527-37. 2004
    ..We have compared the ability of the antipsychotic drugs clozapine and haloperidol, alone and in combination with chronic phencyclidine (PCP), to modulate 5-HT(2A) receptor ..
  99. ncbi Metabolic differences between Asian and Caucasian patients on clozapine treatment
    Mythily Subramaniam
    Institute of Mental Health and Woodbridge Hospital, Singapore, and Department of Psychiatry, University of Melbourne, Richmond, Australia
    Hum Psychopharmacol 22:217-22. 2007
    To establish if there are ethnic differences in the various metabolic disturbances that are common with clozapine treatment.
  100. ncbi Artificial neural network prediction of clozapine response with combined pharmacogenetic and clinical data
    Chao Cheng Lin
    Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taiwan
    Comput Methods Programs Biomed 91:91-9. 2008
    Although one third to one half of refractory schizophrenic patients responds to clozapine, however, there are few evidences currently that could predict clozapine response before the use of the medication...
  101. ncbi Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain
    Gavin P Reynolds
    Department of Biomedical Science, University of Sheffield, UK
    Am J Psychiatry 160:677-9. 2003
    ..The authors determined whether this association held true for weight gain after clozapine treatment.

Research Grants68

  1. NT69L: a potential, novel antischizophrenic drug
    Elliott Richelson; Fiscal Year: 2009
    ..We are hypothesizing that NT69L is similar in its behavioral and in its biochemical effects to clozapine, the classical, atypical antipsychotic drug...
  2. Tyrosine Availability Influences Mesocortico-Limbic Catecholamines
    GEORGE EUGENE JASKIW; Fiscal Year: 2012
    ..Drugs administered will include clozapine and haloperidol, medications used for the treatment of schizophrenia...
  3. Regulation of thyroid hormone levels by central and peripheral pathways
    KRISTEN RACHEL VELLA; Fiscal Year: 2013
    ..DREADDs are mutant receptors that are stimulated only by the pharmacologically inert ligand clozapine-N-oxide (CNO)...
  4. Genetics and Haloperidol Response
    Robert J Hitzemann; Fiscal Year: 2012
    ..The side-effects of the atypical antipsychotic drugs such as clozapine, include diabetes, severe weight gain and cardiac arrhythmias...
  5. Pharmacology of Risperidone Effects on Bone Remodeling and Energy Metabolism
    Karen L Houseknecht; Fiscal Year: 2013
    ..functional consequence of specific receptor binding effects of RIS, and prolactin-sparing SGAs olanzapine and clozapine, using osteoblast and osteoclast culture in vitro, and in vivo by using established mouse models of RIS-induced ..
  6. Aging and Antipsychotic Efficacy - Epigenetic Mechanisms
    Hongxin Dong; Fiscal Year: 2013
    ..young (3-month old) and aged (24-month old) mice will be treated with haloperidol (HAL, a typical) or clozapine (CLZ, an atypical) alone or in combination with the HDAC1-specific inhibitor entinostat (MS-275) or pan-HDAC ..
  7. Oxidative stress and schizophrenia: combination of cell biology and brain imaging
    Akira Sawa; Fiscal Year: 2013
    ..Excess ROS in SZ was partially normalized by clozapine, which is utilized clinically in treatment of patients with SZ...
  8. Negative symptoms of schizophrenia: animal models
    Athina Markou; Fiscal Year: 2013
    ..Our extensive Preliminary Studies showed that clozapine, but not quetiapine, partially attenuated repeated PCP-induced deficits in attention and response inhibition in ..
  9. Effect of Atypical Antipsychotics on Fructose Metabolism and Weight Gain
    CAROLINE PALAVICINO-MAGGIO; Fiscal Year: 2012
    ..serotonin and histamine receptors are expressed in the intestine;(2) our preliminary result that chronic clozapine treatment increases intestinal fructose uptake in C57BL/6 wild type mice;(3) our preliminary result that wild ..
  10. Mechanisms of schizophrenia-like phenotypes in BACE 1 knockout mice
    Alena Savonenko; Fiscal Year: 2010
    ..Importantly, some of these symptoms were responsive to clozapine treatment...
  11. Development of Novel Agents for CNS-related Diseases
    Seth Y Ablordeppey; Fiscal Year: 2012
    ..Atypical Antipsychotic Agents (AAAs) or Second Generation Antipsychotics (SGAs), typified by clozapine and olanzapine, have replaced typical antipsychotic agents (TAAs) as the drugs of choice for the treatment of ..
  12. In Vivo Neuronal Modulation via Engineered G Protein-Coupled Receptors
    SARAH CLAIRE ROGAN; Fiscal Year: 2012
    ..any detectable intrinsic activity, and are selectively activated by the bioavailable inert synthetic ligand, clozapine-N-oxide (CNO)...
  13. Effect of chronic antipsychotic medication administration on cocaine poisoning
    KENNON JAMES HEARD; Fiscal Year: 2010
    ..density in mice treated for 28 days with continuous infusions of clinically relevant APMs (haloperidol, clozapine, ziprasidone, and aripiprazole) or placebo...
  14. GABA and Early Intervention of Schizophrenia
    Tsung Ung W Woo; Fiscal Year: 2010
    ..the peri-onset period, or placebo, added onto their regimen of second-generation antipsychotics, excluding clozapine. We will use a 2-back WM task and the WM sub-tests of the MATRICS (Measurement and Treatment Research to Improve ..
  15. Alcoholism and Schizophrenia: A Translational Approach to Treatment
    Alan I Green; Fiscal Year: 2012
    ..available antipsychotic medications do not limit alcohol use in patients with SCZ, the atypical antipsychotic clozapine (CLOZ) appears to do so...
  16. Innovative Intervention Strategies for Metabolic Problems in Schizophrenia
    Xiaoduo Fan; Fiscal Year: 2012
    ..randomized, double-blind, placebo-controlled trial of telmisartan 80 mg/day, as an adjunctive therapy in 70 clozapine or olanzapine treated schizophrenia patients...
  17. Endogenous Kynurenic Acid Modulates Prefrontal ACh Levels and Cognitive Behavior
    Robert Schwarcz; Fiscal Year: 2013
    ..effects will be evaluated both in control animals and in rats treated with typical (haloperidol) or atypical (clozapine) neuroleptic drugs in combination with an adjunctive therapy targeting the 17nAChR with a clinically used ..
  18. Prodrugs of NAAG Peptidase Inhibitors for the Treatment of Schizophrenia
    Jia Zhou; Fiscal Year: 2009
    ..Atypical antipsychotic drugs, such as clozapine, risperidone, and olanzapine are widely used to treat schizophrenia but are not fully effective in moderating ..
  19. Mechanism of 5HT2AR regulation by Egr3
    AMELIA GALLITANO; Fiscal Year: 2013
    ..Moreover, their reduced sensitivity to the sedating effects of clozapine, compared with wildtype (WT) littermates, parallels the unexplained clinical observation that schizophrenia ..
  20. Physiological Implications of Serotonin Receptor Regulation
    Laura M Bohn; Fiscal Year: 2013
    ..For example, the atypical antipsychotic drug clozapine was designed to block the activity of this receptor...
  21. Neural pathway of REM sleep atonia
    Jun Lu; Fiscal Year: 2013
    ..which modified G coupled cholinergic receptors are inserted into the neurons that are only activated by activate clozapine-N-oxide (CNO)...
  22. Effects of Clopazine and haloperidol on responding
    Danielle Gulick; Fiscal Year: 2010
    ..In patients with SCZ and in the hamster, the atypical antipsychotic clozapine (CLOZ) dramatically decreases alcohol consumption but the typical antipsychotic haloperidol (HAL) does not...
  23. Understanding the Metabolic Impact of Aldehyde Oxidase on New Drug Design
    Jeffrey P Jones; Fiscal Year: 2013
    ..From the inhibition results, we are able to determine that two compounds, clozapine and chlorpromazine, have high enough affinities to show drug-drug interactions...
  24. A novel, transient inactivation technique for studying the primate social brain
    Christopher J Machado; Fiscal Year: 2013
    ..These novel receptors are triggered by intravenous or oral administration of a nontoxic molecule called clozapine-N-oxide (CNO)...
  25. DRUG METABOLISM BY INTESTINAL FLAVIN MONOOXYGENASES
    ROSITA PROTEAU; Fiscal Year: 2001
    ..The FMO system oxidizes a wide range of pharmaceuticals such as tamoxifen, imipramine, chlorpromazine, clozapine, and albendazole, all of which have low bioavailability...
  26. Investigating astrocytic Gq-GPCR and Ca2+ signaling in functional hyperemia in vi
    Daniel Bonder; Fiscal Year: 2013
    ..does not respond to endogenous ligands and instead is activated by the blood-brain barrier-permeable compound, Clozapine-N-Oxide (CNO);CNO does not activate endogenous receptors...
  27. Structure/Function Studies of Quinone Reductase 2
    Zhongtao Zhang; Fiscal Year: 2009
    ..of QR2 polymorphism in relationship with certain neurological diseases, as QR2 polymorphism has been associated with idiopathic Parkinson's disease, schizophrenia, alcohol withdrawal symptoms and clozapine-induced aranulocytosis.
  28. Development of Ultrafine Particles for Intranasal Delivery of Antipsychotics
    SANDRA EDITH NORIEGA; Fiscal Year: 2013
    ..project is to develop a biocompatible ultrafine particle-based vector system for the intranasal delivery of clozapine for the pharmacological therapy of treatment- resistant schizophrenic disorders and their associated suicidal ..
  29. Clozapine Sensors for Improving Therapeutic Treatments of Schizophrenia
    Karen Wu; Fiscal Year: 2011
    ..It is estimated that 20% to 60% of patients have treatment-resistant schizophrenia. Clozapine remains the only effective antipsychotic for treatment-resistant schizophrenia despite the risks of toxic side ..
  30. Structure and function of the 5HT2A/mGluR2 complex in schizophrenia
    Javier Gonzalez-Maeso; Fiscal Year: 2013
    ..Notably, clozapine and other atypical antipsychotics have high affinity for serotonin 5-HT2A receptors (2AR), and metabotropic ..
  31. Dissecting hypothalamic pathways that regulate sexually dimorphic behaviors
    NIRAO MAHESH SHAH; Fiscal Year: 2013
    ..In Aim 3, we will utilize a Cre- dependent heterologous receptor (DREADD) activated by a heterologous ligand (clozapine-N-oxide) to switch on activity in these VMH neurons in vivo in males and females...
  32. Dissecting Heterogeneity of Treatment Response of First Episode Schizophrenia
    Anil K Malhotra; Fiscal Year: 2012
    ..effects, in the context of a standardized, open-label treatment algorithm with risperidone and aripiprazole (or clozapine in treatment refractory patients) for the remainder of a total 52-week study period...
  33. MOTOR EFFECTS OF ATYPICAL ANTIPSYCHOTICS
    John Salamone; Fiscal Year: 2003
    DESCRIPTION: (Verbatim from the Applicant's Abstract) Clozapine is an antipsychotic drug with a unique clinical, biochemical and behavioral profile...
  34. Clozapine for Cannabis Use Disorder in Schizophrenia
    Alan I Green; Fiscal Year: 2013
    ..Moreover, the one antipsychotic that preliminary data suggest may well limit cannabis use in these patients, clozapine (CLOZ), is not used for this purpose;it is reserved for patients whose psychosis is treatment resistant...
  35. Adjunctive Minocycline in Clozapine Treated Patients for Psychosis and Cognition
    Deanna L Kelly; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Over 60% of people treated with clozapine continue to have persistent symptoms and cognitive impairments and little data is available to support evidence-based recommendations to guide clinicians in ..
  36. CELLULAR MECHANISMS OF DRUG REACTIONS IN SCHIZOPHRENIA
    Edmond Yunis; Fiscal Year: 1999
    DESCRIPTION (Adapted from applicant's abstract): There are different HLA associations in patients with clozapine-induced agranulocytosis (CA): in Jewish patients, HLA-B38, DR4 (DRB1*0402, DQB1*0302, DQA1*0301, DPB1*0401), HSP70 9...
  37. Developmental Psychopharmacology of Antipsychotics
    JENNY WILEY; Fiscal Year: 2007
    ..Research on the effects of atypical antipsychotics (e.g., clozapine) that do not produce extrapyramidal motor effects is particularly lacking...
  38. Acute Inhibition of Adult-born Granule Cells and its Effect on Antidepressant Act
    LINDSAY ELSA TANNENHOLZ; Fiscal Year: 2013
    ..evolved G-protein coupled receptor (hM4Di), which is exclusively activated by the pharmacologically inert drug clozapine-N-oxide (CNO), selectively in adult-generated GCs...
  39. Acute Impact of Antipsychotics on Insulin Sensitivity: A Novel Human Model
    Jonathan Meyer; Fiscal Year: 2009
    ..use certain medications, and 2) facilitating the development of antipsychotics with the efficacy of agents like clozapine, but free of the metabolic liability...
  40. GABA AGONIST THERAPY IN TARDIVE DYSKINESIA
    Carol Tamminga; Fiscal Year: 1999
    ..In addition, we have demonstrated a therapeutic effect of clozapine in TD and now are seeking to understand whether clozapine improves dyskinesias in TD through diminishing these ..
  41. Cannabis and Schizophrenia: Self-Medication and Agonist Treatment?
    Alan I Green; Fiscal Year: 2010
    ..medication that preliminary studies have shown to have some ability to limit cannabis use in these patients, clozapine, has substantial toxicity and is thus used by only a small percentage of patients who might benefit from it...
  42. CANNABIS AND SCHIZOPHRENIA: CLOZAPINE VS RISPERIDONE
    Alan Green; Fiscal Year: 2005
    ..Preliminary data suggest that the atypical antipsychotic drug clozapine (CLOZ), currently used primarily for treatment resistant patients, may limit cannabis use in "dual diagnosis" ..
  43. Clozapine, cannabis and first episode schizophrenia
    Alan Green; Fiscal Year: 2003
    ..and large-scale investigations of novel antipsychotics in first episode patients are underway, the novel drug clozapine (CLOZ) is not used clinically or in most research studies in patients because of Its side effects and the ..
  44. NEUROLEPTIC-INDUCED DYSKINESIAS AND DYSTONIAS
    Gaylord Ellison; Fiscal Year: 1992
    ..While "atypical" neuroleptics (clozapine and raclopride) do not induce these syndromes, with clozapine it seems that the TD-like profile gradually ..
  45. Cannabis & Schizophrenia: fMRI Reward Circuit Biomaker
    Alan Green; Fiscal Year: 2005
    ..use in these patients, preliminary data from our group and others suggest that the atypical antipsychotic drug clozapine (CLOZ) may limit cannabis use in patients with SCHIZ much more effectively than do either typical antipsychotics ..
  46. ANTIPSYCHOTIC DRUGS AND CONTROL OF DOPAMINERGIC NEURONS
    Robert Roth; Fiscal Year: 2006
    ..The atypical APD, clozapine, is effective in reversing the cognitive impairment and normalizing PFC DA turnover in the PCP dysregulated ..
  47. ANTIPSYCHOTICS AND RECEPTOR DESENSITIZATION MACHINERY
    Eugenia Gurevich; Fiscal Year: 2002
    ..of the effects of acute and subchronic treatment with typical antipsychotic haloperidol and atypical drug clozapine on the expression of arrestin and GRK mRNAs and proteins in various brain areas implicated in schizophrenia ..
  48. Atypical Antipsychotics: Determinants of Concentration
    Bruce Pollock; Fiscal Year: 2004
    ..exposure of the antipsychotics (risperidone, olanzapine, ziprasidone, fluphenazine, perphenazine, and clozapine) using mixed effect population pharmacokinetic methodologies...
  49. ATYPICAL ANTIPSYCHOTICS AND P50 GATING IN SCHIZOPHRENIA
    Lawrence Adler; Fiscal Year: 2001
    ..In contrast, treatment with clozapine. a prototypical atypical antipsychotic, has normalized P50 auditory gating in neuroleptic-resistant ..
  50. ANTIPSYCHOTIC TREATMENT IN LATE LIFE SCHIZOPHRENIA
    Jonathan Lacro; Fiscal Year: 2001
    ..Recently, experience with serotonin- dopamine antagonists, or "atypical" antipsychotic medications such as clozapine and risperidone, has shown that is possible to better dissociate the antipsychotic effects of medications from ..
  51. SMOOTH PURSUIT, SACCADES, AND FIXATION IN SCHIZOPHRENIA
    Lee Friedman; Fiscal Year: 1992
    ..withdrawal from medication and after treatment either with typical neuroleptics or the atypical neuroleptic clozapine. Patients with affective disorders have been studied either in the unmedicated condition or during treatment ..
  52. SMOKING, SCHIZOPHRENIA, AND ATYPICAL ANTIPSYCHOTICS
    Joseph McEvoy; Fiscal Year: 1999
    ..decreases significantly when patients switch from haloperidol to pharmacotherapy with atypical antipsychotic, clozapine. Nicotine corrects certain deficits in sensory gating and cognitive psychomotor performance that are not ..
  53. GLYCINE AND D-CYCLOSERINE IN SCHIZOPHRENIA
    Donald Goff; Fiscal Year: 2000
    DESCRIPTION (Applicant's Abstract): Clozapine is more effective for negative symptoms of schizophrenia than conventional neuroleptics, but the neurochemical actions contributing to this superior clinical efficacy remain unclear...
  54. MONOAMINERGIC MODULATION OF PREFRONTAL CORTEX
    DALTON SURMEIER; Fiscal Year: 2004
    ..In part, the clinical effectiveness of atypical neuroleptics like clozapine has motivated this new line of thought...
  55. Drug-Induced Lipid Accumulation in C. elegans
    Donard Dwyer; Fiscal Year: 2006
    ..elegans. Furthermore, tph-1 mutants treated with clozapine, an antipsychotic drug with weight gain liability, accumulated lipid and arrested without reaching sexual ..
  56. DOPAMINE SYSTEM INTERACTIONS AND SCHIZOPHRENIA
    ARIEL DEUTCH; Fiscal Year: 2004
    ..These studies will determine the efferent targets of PVT neurons that are activated by clozapine and psychostimulants, determine if the Fos response of PVT neurons occurs in D3 receptor-expressing cells, and ..
  57. CLOZAPINE INDUCED AGRANULOCYTOSIS IN SCHIZOPHRENIA
    Stanton Gerson; Fiscal Year: 1992
    b>Clozapine is a unique, atypical antipsychotic dibenzoxazebine with unusual efficacy in treating patients with refractory schizophrenia. Randomized studies have shown it to be superior to conventional treatment of this disorder...
  58. Neurosteroids and Schizophrenia
    Christine Marx; Fiscal Year: 2005
    ..We have also demonstrated that acute olanzapine and clozapine administration alters cerebral cortical neurosteroids in rodents...
  59. RISPERIDONE AND CLOZAPINE IN CHRONIC SCHIZOPHRENIA
    Jeffrey Lieberman; Fiscal Year: 1999
    ..Standard antipsychotic drugs are clinically effective in only 50% of the patients. The atypical antipsychotic clozapine (CLO) is the only treatment with proven efficacy in refractory patients...
  60. RISPERIDONE AND CLOZAPINE IN CHRONIC SCHIZOPHRENIA
    Jan Volavka; Fiscal Year: 1999
    ..Standard antipsychotic drugs are clinically effective in only 50% of the patients. The atypical antipsychotic clozapine (CLO) is the only treatment with proven efficacy in refractory patients...
  61. SEROTONERGIC MODULATION OF AMYGDALOID TRANSMISSION
    Donald Rainnie; Fiscal Year: 2001
    ..Lesions of the amygdala induce a permanent disruption of APDs, such as clozapine, are particularly efficacious in treating negative symptoms of schizophrenia...
  62. Antipsychotics: Temporal Effects on Cognitive Function
    Alvin Terry; Fiscal Year: 2006
    ..neuroleptics such as haloperidol (in a temporally dependent fashion), but not atypical agents such as clozapine, leads to cognitive impairment and that a reduction in a key marker for cholinergic neurons, choline ..
  63. Ampakines in Schizophrenia
    Steven Johnson; Fiscal Year: 2002
    ..We recently completed an exploratory safety trial of the AMPAKINE CX516 added to clozapine in 19 treatment-resistant patients...
  64. SEROTONIN IN TREATMENT REFRACTORY SCHIZOPHRENIA
    Rene Kahn; Fiscal Year: 1990
    ..b>Clozapine is the only compound proven to be effective in this group of treatment refractory schizophrenics...
  65. Clozapine Treatment of Schizophrenic Patients
    Robert Buchanan; Fiscal Year: 2006
    This is a submission of a competitive renewal application, MH 45074: "Clozapine Treatment of Schizophrenic Outpatients"...
  66. ECT IN CLOZAPINE REFRACTORY SCHIZOPHRENIA
    Georgios Petrides; Fiscal Year: 2003
    ..b>Clozapine represents a unique treatment in our armamentarium for schizophrenia as it is helpful in treating 30-50% of the ..
  67. Clozapine Drug Discrimination in C57BL/6J Mice
    SCOTT PHILIBIN; Fiscal Year: 2005
    b>Clozapine is the prototypical atypical antipsychotic drug and represents a tremendous improvement over conventional antipsychotics in terms of therapeutic efficacy and reduced side effect liability for the treatment of schizophrenia...
  68. CLOZAPINE AND SKILL TRAINING FOR SCHIZOPHRENIA
    Thomas Smith; Fiscal Year: 2000
    ..and c) conduct a research project studying the combined effects of the atypical antipsychotic medication clozapine and a manualized symptom management social skills training program on symptom control, social skill, and social ..