L E Schechter

Summary

Affiliation: Wyeth Research
Country: USA

Publications

  1. ncbi request reprint Differentiating antidepressants of the future: efficacy and safety
    Sharon Rosenzweig-Lipson
    Wyeth Discovery Neuroscience, Depression and Anxiety, CN 8000, Princeton, NJ 08543, USA
    Pharmacol Ther 113:134-53. 2007
  2. ncbi request reprint Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466
    Lee E Schechter
    Discovery Neuroscience, Wyeth Research, Princeton, NJ 08543 8000, USA
    Neuropsychopharmacology 33:1323-35. 2008
  3. ncbi request reprint Lecozotan (SRA-333): a selective serotonin 1A receptor antagonist that enhances the stimulated release of glutamate and acetylcholine in the hippocampus and possesses cognitive-enhancing properties
    L E Schechter
    Wyeth, Neuroscience Discovery Research, Princeton, NJ 08543, USA
    J Pharmacol Exp Ther 314:1274-89. 2005
  4. pmc Innovative approaches for the development of antidepressant drugs: current and future strategies
    Lee E Schechter
    Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA
    NeuroRx 2:590-611. 2005
  5. ncbi request reprint 1,2,5-Thiadiazole derivatives are potent and selective ligands at human 5-HT1A receptors
    A L Sabb
    Medicinal Chemistry, Chemical Sciences, Wyeth Ayerst Research, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 11:1069-71. 2001
  6. pmc Effects of chronic fluoxetine treatment in the presence and absence of (+/-)pindolol: a microdialysis study
    L A Dawson
    Neuroscience Research, Wyeth Ayerst, CN8000, Princeton, New Jersey, 08543 8000, USA
    Br J Pharmacol 130:797-804. 2000
  7. ncbi request reprint Effect of chronic fluoxetine and WAY-100635 treatment on serotonergic neurotransmission in the frontal cortex
    L A Dawson
    Neuroscience Research, Wyeth Ayerst, Princeton, NJ, USA
    J Psychopharmacol 16:145-52. 2002
  8. ncbi request reprint Characterization of 5-HT1A receptor functional coupling in cells expressing the human 5-HT1A receptor as assessed with the cytosensor microphysiometer
    J Dunlop
    Wyeth Ayerst Research, CNS Disorders, Princeton, New Jersey 08543, USA
    J Pharmacol Toxicol Methods 40:47-55. 1998
  9. pmc Preclinical characterization of WAY-211612: a dual 5-HT uptake inhibitor and 5-HT (1A) receptor antagonist and potential novel antidepressant
    C E Beyer
    Discovery Neuroscience, Wyeth Research, Princeton, NJ 08543 8000, USA
    Br J Pharmacol 157:307-19. 2009
  10. ncbi request reprint The potential utility of 5-HT1A receptor antagonists in the treatment of cognitive dysfunction associated with Alzheimer s disease
    L E Schechter
    Wyeth Ayerst Research, Wyeth Neuroscience, CN 8000, Princeton, NJ 08543 8000, USA
    Curr Pharm Des 8:139-45. 2002

Detail Information

Publications47

  1. ncbi request reprint Differentiating antidepressants of the future: efficacy and safety
    Sharon Rosenzweig-Lipson
    Wyeth Discovery Neuroscience, Depression and Anxiety, CN 8000, Princeton, NJ 08543, USA
    Pharmacol Ther 113:134-53. 2007
    ..This review will discuss the many facets of differentiation and potential strategies for the development of novel antidepressants...
  2. ncbi request reprint Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466
    Lee E Schechter
    Discovery Neuroscience, Wyeth Research, Princeton, NJ 08543 8000, USA
    Neuropsychopharmacology 33:1323-35. 2008
    ....
  3. ncbi request reprint Lecozotan (SRA-333): a selective serotonin 1A receptor antagonist that enhances the stimulated release of glutamate and acetylcholine in the hippocampus and possesses cognitive-enhancing properties
    L E Schechter
    Wyeth, Neuroscience Discovery Research, Princeton, NJ 08543, USA
    J Pharmacol Exp Ther 314:1274-89. 2005
    ..m.) in marmosets. The heterosynaptic nature of the effects of lecozotan imbues this compound with a novel mechanism of action directed at the biochemical pathologies underlying cognitive loss in Alzheimer's disease...
  4. pmc Innovative approaches for the development of antidepressant drugs: current and future strategies
    Lee E Schechter
    Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA
    NeuroRx 2:590-611. 2005
    ..The present review addresses the most exciting approaches and reviews the localization, neurochemical and behavioral data that provide the supporting rationale for each of these targets or target combinations...
  5. ncbi request reprint 1,2,5-Thiadiazole derivatives are potent and selective ligands at human 5-HT1A receptors
    A L Sabb
    Medicinal Chemistry, Chemical Sciences, Wyeth Ayerst Research, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 11:1069-71. 2001
    ....
  6. pmc Effects of chronic fluoxetine treatment in the presence and absence of (+/-)pindolol: a microdialysis study
    L A Dawson
    Neuroscience Research, Wyeth Ayerst, CN8000, Princeton, New Jersey, 08543 8000, USA
    Br J Pharmacol 130:797-804. 2000
    ..This may suggest that the clinical augmentation of antidepressant action by pindolol, when co-administered with a SSRI, is via antagonism of the 5-HT(1A) receptor...
  7. ncbi request reprint Effect of chronic fluoxetine and WAY-100635 treatment on serotonergic neurotransmission in the frontal cortex
    L A Dawson
    Neuroscience Research, Wyeth Ayerst, Princeton, NJ, USA
    J Psychopharmacol 16:145-52. 2002
    ..These data suggest that augmentation of an SSRI by combined pharmacotherapy with a 5-HT1A antagonist would be effective upon prolonged exposure...
  8. ncbi request reprint Characterization of 5-HT1A receptor functional coupling in cells expressing the human 5-HT1A receptor as assessed with the cytosensor microphysiometer
    J Dunlop
    Wyeth Ayerst Research, CNS Disorders, Princeton, New Jersey 08543, USA
    J Pharmacol Toxicol Methods 40:47-55. 1998
    ..The evaluation of 5-HT1A ligands using the microphysiometer, which represents a very distinct indice of 5-HT1A receptor function compared with the cAMP assay, results in a different profile of functional activity...
  9. pmc Preclinical characterization of WAY-211612: a dual 5-HT uptake inhibitor and 5-HT (1A) receptor antagonist and potential novel antidepressant
    C E Beyer
    Discovery Neuroscience, Wyeth Research, Princeton, NJ 08543 8000, USA
    Br J Pharmacol 157:307-19. 2009
    ....
  10. ncbi request reprint The potential utility of 5-HT1A receptor antagonists in the treatment of cognitive dysfunction associated with Alzheimer s disease
    L E Schechter
    Wyeth Ayerst Research, Wyeth Neuroscience, CN 8000, Princeton, NJ 08543 8000, USA
    Curr Pharm Des 8:139-45. 2002
    ....
  11. ncbi request reprint Studies towards the next generation of antidepressants. Part 1: Indolylcyclohexylamines as potent serotonin reuptake inhibitors
    K L Meagher
    Global Chemical Sciences and Neuroscience Departments, Wyeth-Ayerst Research Laboratories, CN 8000, NJ 08543-8000, Princeton, USA
    Bioorg Med Chem Lett 11:1885-8. 2001
    ..A series of indolylcyclohexylamines possessing potent and selective serotonin reuptake inhibition is reported. The most interesting compounds proved to have subnanomolar 5-HT transporter activity, and exhibited moderate 5-HT(1A) affinity...
  12. ncbi request reprint Novel pyridyl-fused 3-amino chroman derivatives with dual action at serotonin transporter and 5-HT1A receptor
    Dahui Zhou
    Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Bioorg Med Chem Lett 17:3117-21. 2007
    ..The compounds described were evaluated for dual 5-HT transporter inhibitory and 5-HT(1A) receptor activities. The design strategy, synthesis, and in vitro biological characterization for these novel compounds are described...
  13. ncbi request reprint Drug development for CNS disorders: strategies for balancing risk and reducing attrition
    Menelas N Pangalos
    Wyeth Research, Neuroscience Discovery, CN800, Princeton, New Jersey 08543, USA
    Nat Rev Drug Discov 6:521-32. 2007
    ....
  14. ncbi request reprint Novel 1-(azacyclyl)-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines as 5-HT6 agonists and antagonists
    Hassan Elokdah
    Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
    Bioorg Med Chem 15:6208-26. 2007
    ....
  15. ncbi request reprint Anxiolytic-like activity of the non-selective galanin receptor agonist, galnon
    S Johannes R Rajarao
    Depression and Anxiety Research, Discovery Neuroscience, Wyeth Research, CN8000, Princeton, NJ 08543, USA
    Neuropeptides 41:307-20. 2007
    ..Moreover, these data indicate rodent GALR1 receptors do not mediate galnon's in vivo activity...
  16. ncbi request reprint Increasing the levels of insulin-like growth factor-I by an IGF binding protein inhibitor produces anxiolytic and antidepressant-like effects
    Jessica E Malberg
    Wyeth Research, Discovery Neuroscience, Princeton, NJ, USA
    Neuropsychopharmacology 32:2360-8. 2007
    ..The present studies demonstrate that an IGFBP inhibitor mimics the behavioral effects of IGF-I and that IGFBP inhibition may represent a novel mechanism by which to increase IGF-I to treat depression and anxiety...
  17. ncbi request reprint A novel approach for predicting antidepressant-induced sexual dysfunction in rats
    Stacey J Sukoff Rizzo
    Depression and Anxiety Research, Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Psychopharmacology (Berl) 195:459-67. 2008
    ..Sexual dysfunction is associated with antidepressant discontinuation. Therefore, there is a need for models that predict antidepressant-induced sexual dysfunction...
  18. ncbi request reprint From menarche to menopause: exploring the underlying biology of depression in women experiencing hormonal changes
    Darlene Deecher
    Wyeth Research, 500 Arcola Rd, RN3164, Collegeville, PA 19426, USA
    Psychoneuroendocrinology 33:3-17. 2008
    ..A testable hypothesis will be proposed to advance our understanding of hormonal effects on mood...
  19. ncbi request reprint Discovery of N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine as a potent, selective, and orally active 5-HT(6) receptor agonist
    Derek C Cole
    Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 50:5535-8. 2007
    ....
  20. doi request reprint A regiospecific synthesis of a series of 1-sulfonyl azepinoindoles as potent 5-HT6 ligands
    Kevin G Liu
    Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 18:3929-31. 2008
    ..A regiospecific synthesis of a series of 1-sulfonyl azepinoindoles as potent 5-HT6 ligands is reported...
  21. doi request reprint Studies toward the discovery of the next generation of antidepressants. Part 6: Dual 5-HT1A receptor and serotonin transporter affinity within a class of arylpiperazinyl-cyclohexyl indole derivatives
    Dahui Zhou
    Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Bioorg Med Chem 16:6707-23. 2008
    ..The best example from this study, 5-(piperazin-1-yl)quinoline analog (trans-20), exhibited equal binding affinities at 5-HT transporter (K(i)=4.9nM), 5-HT(1A) receptor (K(i)=6.2nM) and functioned as a 5-HT(1A) receptor antagonist...
  22. pmc Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments
    Darrick T Balu
    Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Brain Res 1211:37-43. 2008
    ....
  23. doi request reprint WAY-200070, a selective agonist of estrogen receptor beta as a potential novel anxiolytic/antidepressant agent
    Zoe A Hughes
    Discovery Neuroscience, Wyeth Research, CN8000, Princeton, NJ 08543, USA
    Neuropharmacology 54:1136-42. 2008
    ....
  24. doi request reprint Inhibition of uptake 2 (or extraneuronal monoamine transporter) by normetanephrine potentiates the neurochemical effects of venlafaxine
    Zia Rahman
    Wyeth Research, Discovery Neuroscience, Depression and Anxiety Disorders, CN 8000, Princeton, NJ 08543 8000, USA
    Brain Res 1203:68-78. 2008
    ....
  25. doi request reprint Pharmacology of neuropeptide S in mice: therapeutic relevance to anxiety disorders
    Sarah K Leonard
    Depression and Anxiety Disorders, Discovery Neuroscience, Wyeth Research, CN8000, Princeton, NJ 08543, USA
    Psychopharmacology (Berl) 197:601-11. 2008
    ..Neuropeptide S (NPS) and its receptor (NPSR) comprise a recently deorphaned G protein-coupled receptor system. Recent reports implicate NPS in the mediation of anxiolytic-like activity in rodents...
  26. doi request reprint Correlating efficacy in rodent cognition models with in vivo 5-hydroxytryptamine1a receptor occupancy by a novel antagonist, (R)-N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane carboxamide (WAY-101405)
    Warren D Hirst
    Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
    J Pharmacol Exp Ther 325:134-45. 2008
    ..These results further support the rationale for use of this compound class in the treatment of cognitive dysfunction associated with psychiatric and neurological conditions...
  27. ncbi request reprint Synthesis and biological evaluation of novel compounds within a class of 3-aminochroman derivatives with dual 5-HT1A receptor and serotonin transporter affinity
    Nicole T Hatzenbuhler
    Chemical and Screening Sciences and Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA
    J Med Chem 49:4785-9. 2006
    ..26a was found to be the most potent and selective compound in this series and was shown to possess neurochemical activity in vivo by producing acute and rapid increases in 5-HT in the rat frontal cortex...
  28. ncbi request reprint WAY-100635 antagonist-induced plasticity of 5-HT receptors: regulatory differences between a stable cell line and an in vivo native system
    Xavier Z Khawaja
    Neuroscience, Wyeth Research, Princeton, New Jersey, USA
    J Neurochem 98:134-45. 2006
    ..This suggests that an antagonist can influence 5-HT(1A) receptor recycling in vitro differently to in vivo regulatory conditions...
  29. ncbi request reprint Studies toward the discovery of the next generation of antidepressants. 3. Dual 5-HT1A and serotonin transporter affinity within a class of N-aryloxyethylindolylalkylamines
    Richard E Mewshaw
    Chemical and Screening Sciences and Neuroscience Discovery Research, Wyeth Research, P O Box 42528, Philadelphia, PA 19101 2528, USA
    J Med Chem 47:3823-42. 2004
    ..5 nM for the 5-HT transporter, respectively. Unfortunately, similar to our previous series (3), compounds in this report also had high affinity for the alpha(1) receptor...
  30. ncbi request reprint Regulators of G-protein signaling 4: modulation of 5-HT1A-mediated neurotransmitter release in vivo
    Chad E Beyer
    Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Brain Res 1022:214-20. 2004
    ....
  31. ncbi request reprint Novel aryloxy-8-azabicyclo[3.2.1]oct-3-enes with 5-HT transporter and 5-HT1A affinity
    Adam M Gilbert
    Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965 1215, USA
    Bioorg Med Chem Lett 14:5281-4. 2004
    ..2nM, 25: 0.54nM, 27: 0.38nM) and good 5-HT(1A) affinity/antagonism (5-HT(1A)K(i), [(35)S]GTPgammaS: E(max) (%): 21: 111.1nM, 0%; 25: 173.2nM, 0%; 27: 107nM, 0%)...
  32. ncbi request reprint 1-(2-Aminoethyl)-3-(arylsulfonyl)-1H-indoles as novel 5-HT6 receptor ligands
    Ronald Bernotas
    Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
    Bioorg Med Chem Lett 14:5499-502. 2004
    ..7 and 5.7 nM, respectively...
  33. ncbi request reprint N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists
    Derek C Cole
    Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 15:379-83. 2005
    ..4 and 3.0 nM affinity, respectively, and antagonized the production of adenylate cyclase at sub-nanomolar concentrations...
  34. ncbi request reprint Studies toward the discovery of the next generation of antidepressants. Part 2: incorporating a 5-HT(1A) antagonist component into a class of serotonin reuptake inhibitors
    Richard E Mewshaw
    Global Chemical Sciences and Neuroscience Departments, Wyeth Ayerst Research Laboratories, PO Box 42528, Philadelphia, PA 19101 2528, USA
    Bioorg Med Chem Lett 12:307-10. 2002
    ..The design and synthesis of a novel series of indole derivatives (9) having dual 5-HT transporter reuptake and 5-HT(1A) antagonist activity are described...
  35. ncbi request reprint Increasing hippocampal neurogenesis: a novel mechanism for antidepressant drugs
    Jessica E Malberg
    Neuroscience Discovery, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Curr Pharm Des 11:145-55. 2005
    ..In addition, the ability of novel compounds to be tested for the neurogenic potential may become an additional way to evaluate a compound for putative antidepressant effects...
  36. ncbi request reprint Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists
    Derek C Cole
    Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 48:353-6. 2005
    ..Within this class, several of the (R)-enantiomers were potent agonists having EC(50) values of 1 nM or less and functioning as full agonists while the (S)-enantiomers displayed moderate antagonist activity...
  37. ncbi request reprint Studies towards the next generation of antidepressants. Part 4: derivatives of 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine with affinity for the serotonin transporter and the 5-HT1A receptor
    Deborah A Evrard
    Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 15:911-4. 2005
    ..Analogs exhibiting affinity for both the serotonin transporter and the 5-HT(1A) receptor are described. Compounds containing 1-(4-indolyl)piperazine and 2-(1H-indol-4-yloxy)ethylamine are promising leads for further SAR studies...
  38. ncbi request reprint Alpha 2A-adrenoceptors enhance the serotonergic effects of fluoxetine
    Chad E Beyer
    Depression and Anxiety Research, Discovery Neuroscience, Wyeth Research, Princeton, NJ 08543, USA
    Eur J Pharmacol 539:164-7. 2006
    ..c.), respectively, did not similarly alter biogenic amine levels. Collectively, these results reveal a specific role for the alpha(2A)-adrenoceptor subtype in augmenting the neurochemical effects of antidepressants...
  39. ncbi request reprint Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications
    Robert H Ring
    Depression and Anxiety Disorders, Discovery Neuroscience, Wyeth Research, CN8000, Princeton, NJ 08543, USA
    Psychopharmacology (Berl) 185:218-25. 2006
    ..Notably, evidence from studies in females has revealed an important role for OT in regulating anxiety behavior...
  40. ncbi request reprint Studies toward the discovery of the next generation of antidepressants. Part 5: 3,4-Dihydro-2H-benzo[1,4]oxazine derivatives with dual 5-HT1A receptor and serotonin transporter affinity
    Dahui Zhou
    Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Bioorg Med Chem Lett 16:1338-41. 2006
    ..The design, synthesis, and structure-activity relationship of two novel classes of benzoxazine derivatives with dual selective serotonin reuptake inhibitors and 5-HT(1A) receptor activities are described...
  41. ncbi request reprint Conformationally constrained N1-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists
    Derek C Cole
    Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 15:4780-5. 2005
    ..Several of the N1-arylsulfonyl-3-(1-methylpyrrolidin-2-ylmethyl)-1H-indole derivatives behave as very potent antagonists ((S)-11r, (S)-11t; IC50 = 0.8, 1.0 nM)...
  42. ncbi request reprint Synthesis and biological evaluation of benzodioxanylpiperazine derivatives as potent serotonin 5-HT(1A) antagonists: the discovery of Lecozotan
    Wayne E Childers
    Chemical and Screening Sciences and Neuroscience, Wyeth Research, CN 8000, Princeton, New Jersey 08543 8000, USA
    J Med Chem 48:3467-70. 2005
    ..Compound 11c (Lecozotan) was selected for further development and is currently in clinical trials...
  43. ncbi request reprint 4-(2-Aminoethoxy)-N-(phenylsulfonyl)indoles as novel 5-HT6 receptor ligands
    Ping Zhou
    Chemical and Screening Science and Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Bioorg Med Chem Lett 15:1393-6. 2005
    ....
  44. doi request reprint Schedule-induced polydipsia: a rat model of obsessive-compulsive disorder
    Brian Platt
    Wyeth Research, Princeton, New Jersey, USA
    Curr Protoc Neurosci . 2008
    ..This protocol describes a rat SIP model of OCD and provides preclinical data for drugs that decrease polydipsia and are clinically effective in the treatment of OCD...
  45. ncbi request reprint Studying rat brain neurochemistry using nanoprobe NMR spectroscopy: a metabonomics approach
    Purnima Khandelwal
    Chemical and Screening Sciences, Discovery Analytical Chemistry and Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, New Jersey 08543 8000, USA
    Anal Chem 76:4123-7. 2004
    ....
  46. ncbi request reprint Nanoprobe NMR spectroscopy and in vivo microdialysis: new analytical methods to study brain neurochemistry
    Purnima Khandelwal
    Chemical and Screening Sciences, Discovery Analytical Chemistry, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    J Neurosci Methods 133:181-9. 2004
    ..To our knowledge, the present experiments are the first to describe the combination of nanoprobe NMR technology with in vivo microdialysis for the analysis of brain neurochemistry in freely-moving rats...
  47. ncbi request reprint Major depressive disorder
    Lee E Schechter
    Curr Pharm Des 11:143-4. 2005