droxidopa

Summary

Summary: A precursor of noradrenaline that is used in the treatment of parkinsonism. The racemic form (DL-threo-3,4-dihydroxyphenylserine) has also been used, and has been investigated in the treatment of orthostatic hypotension. There is a deficit of noradrenaline as well as of dopamine in Parkinson's disease and it has been proposed that this underlies the sudden transient freezing seen usually in advanced disease. Administration of DL-threo-3,4-dihydroxyphenylserine has been claimed to result in an improvement in this phenomenon but controlled studies have failed to demonstrate improvement. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)

Top Publications

  1. ncbi L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience
    Horacio Kaufmann
    Dysautonomia Research Laboratory, New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA
    Clin Auton Res 18:19-24. 2008
  2. ncbi L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure
    C J Mathias
    Neurovascular Medicine Unit, Division of Neuroscience and Psychological Medicine, Imperial College of Science, Technology, and Medicine at St Mary s, London, UK
    Clin Auton Res 11:235-42. 2001
  3. ncbi L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience
    Christopher J Mathias
    Neurovascular Medicine Unit, Faculty of Medicine, Imperial College London at St Mary s Hospital, Praed Street, London, W2 1NY, UK
    Clin Auton Res 18:25-9. 2008
  4. ncbi An explanation of the unexpected efficacy of L-DOPS in pure autonomic failure
    Murray Esler
    Clin Auton Res 14:356-7. 2004
  5. pmc L-threo 3,4-dihydroxyphenylserine treatment during mouse perinatal and rat postnatal development does not alter the impact of dietary copper deficiency
    Joshua W Pyatskowit
    Department of Biochemistry and Molecular Biology, University of Minnesota Medical School Duluth, 1035 University Drive, Duluth, MN 55812, USA
    Nutr Neurosci 8:173-81. 2005
  6. ncbi L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy
    Christopher H Gibbons
    Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Neurology 65:1104-6. 2005
  7. pmc Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors
    John F Cryan
    Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 101:8186-91. 2004
  8. ncbi Norepinephrine precursor therapy in neurogenic orthostatic hypotension
    Horacio Kaufmann
    Mount Sinai School of Medicine, Box 1052, New York, NY 10029, USA
    Circulation 108:724-8. 2003
  9. ncbi [Human striatal D-neurons and their significance]
    Keiko Ikemoto
    Clinical Research Institute, National Minami Hanamaki Hospital, 500, Suwa, Hanamaki, 025 0033 Japan
    Nihon Shinkei Seishin Yakurigaku Zasshi 22:131-5. 2002
  10. ncbi Comment on "Midodrine hydrochloride and L-threo-3,4-dihydroxy-phenylserine preserve cerebral blood flow in hemodialysis patients with orthostatic hypotension" by Fujisaki et al
    Vijay Sharma
    Ther Apher Dial 11:407-8. 2007

Research Grants

Scientific Experts

Detail Information

Publications127 found, 100 shown here

  1. ncbi L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience
    Horacio Kaufmann
    Dysautonomia Research Laboratory, New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA
    Clin Auton Res 18:19-24. 2008
    ..In double blind, cross over, placebo controlled trials, administration of droxidopa, a synthetic amino acid that is decarboxylated to norepinephrine by the enzyme L: -aromatic amino acid ..
  2. ncbi L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure
    C J Mathias
    Neurovascular Medicine Unit, Division of Neuroscience and Psychological Medicine, Imperial College of Science, Technology, and Medicine at St Mary s, London, UK
    Clin Auton Res 11:235-42. 2001
    ..In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF...
  3. ncbi L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience
    Christopher J Mathias
    Neurovascular Medicine Unit, Faculty of Medicine, Imperial College London at St Mary s Hospital, Praed Street, London, W2 1NY, UK
    Clin Auton Res 18:25-9. 2008
    ..L-threo-dihydroxyphenyslerine (Droxidopa) is a pro-drug which has a structure similar to noradrenaline, but with a carboxyl group...
  4. ncbi An explanation of the unexpected efficacy of L-DOPS in pure autonomic failure
    Murray Esler
    Clin Auton Res 14:356-7. 2004
  5. pmc L-threo 3,4-dihydroxyphenylserine treatment during mouse perinatal and rat postnatal development does not alter the impact of dietary copper deficiency
    Joshua W Pyatskowit
    Department of Biochemistry and Molecular Biology, University of Minnesota Medical School Duluth, 1035 University Drive, Duluth, MN 55812, USA
    Nutr Neurosci 8:173-81. 2005
    ..DOPS treatment did not alter this pattern. Although DOPS was present in treated animal's tissues, survival in mice and catecholamine levels in mice and rats were not altered by the 1 mg/ml dose of DOPS...
  6. ncbi L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy
    Christopher H Gibbons
    Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Neurology 65:1104-6. 2005
    ..L-DOPS may benefit patients with severe orthostatic intolerance and be particularly effective in patients with ganglionic NiAchR antibodies...
  7. pmc Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors
    John F Cryan
    Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 101:8186-91. 2004
    ..These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs...
  8. ncbi Norepinephrine precursor therapy in neurogenic orthostatic hypotension
    Horacio Kaufmann
    Mount Sinai School of Medicine, Box 1052, New York, NY 10029, USA
    Circulation 108:724-8. 2003
    ..In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine (NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture...
  9. ncbi [Human striatal D-neurons and their significance]
    Keiko Ikemoto
    Clinical Research Institute, National Minami Hanamaki Hospital, 500, Suwa, Hanamaki, 025 0033 Japan
    Nihon Shinkei Seishin Yakurigaku Zasshi 22:131-5. 2002
    ..of efficacy of pharmacotherapy for Parkinson's disease by uptaking monoamine precursors, including L-dopa or droxidopa (L-threo-DOPS), and by converting them to dopamine (DA) or noradrenaline (NA), respectively...
  10. ncbi Comment on "Midodrine hydrochloride and L-threo-3,4-dihydroxy-phenylserine preserve cerebral blood flow in hemodialysis patients with orthostatic hypotension" by Fujisaki et al
    Vijay Sharma
    Ther Apher Dial 11:407-8. 2007
  11. doi Neurogenic orthostatic hypotension: new prospects in treatment. Introduction
    Horacio Kaufmann
    Clin Auton Res 18:1. 2008
  12. ncbi Case report: Marathon runner with severe autonomic failure
    Emily M Garland
    Autonomic Dysfunction Center, Vanderbilt University, Nashville, TN 37232, USA
    Lancet 366:S13. 2005
  13. ncbi Clinical effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients
    Tadao Akizawa
    Center for Purification Therapy, Wakayama Medical University, Wakayama City, Japan
    Nephron 90:384-90. 2002
    ..These findings indicate that L-DOPS taken before hemodialysis prevents orthostatic hypotension in patients undergoing hemodialysis, and is also effective for the interdialytic symptoms related to orthostatic hypotension...
  14. ncbi Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline
    S A Thomas
    Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle 98195 7370, USA
    Nature 387:94-7. 1997
    ..The unexpected increase in basal metabolic rate is not due to hyperthyroidism, compensation by the widely expressed uncoupling protein UCP2, or shivering...
  15. ncbi Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure
    David S Goldstein
    Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, MD 20892 1620, USA
    Clin Auton Res 14:363-8. 2004
    ....
  16. ncbi Behavior of fluorinated analogs of L-(3,4-dihydroxyphenyl)alanine and L-threo-(3,4-dihydroxyphenyl)serine as substrates for Dopa decarboxylase
    Carla Borri Voltattorni
    Dipartimento di Scienze Neurologiche e della Visione, Sezione di Chimica Biologica, Facolta di Medicina e Chirurgia, Universita degli Studi di Verona, Verona, Italy
    Biochem Biophys Res Commun 295:107-11. 2002
    ..Condensation of fluorinated catecholamines and catechol amino acids with endogenous aldehydes will be investigated as an approach to study possible mechanisms of L-Dopa-linked neurotoxicity...
  17. ncbi [Simple method for precognition of drug interaction between oral iron and phenolic hydroxyl group-containing drugs]
    Nobuyoshi Sunagane
    Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda City 278 8510, Japan
    Yakugaku Zasshi 125:197-203. 2005
    ..When a levodopa or droxidopa preparation, judged as grade 3 in screening, was concomitantly administered with an iron preparation, a ..
  18. ncbi [Pure akinesia presenting with antecollis]
    Satoru Ota
    Department of Neurology, Tokyo Metropolitan Matsuzawa Hospital, 2 1 1 Kamikitazawa, Setagaya Ku, Tokyo 156 0057, Japan
    No To Shinkei 57:893-8. 2005
    ..This is the first case of antecollis induced by L-DOPS in a pure akinesia patient, providing important information on mechanism of drug induced dystonia and indicating caution in the clinical use of L-DOPS...
  19. ncbi Effects of dopaminergic agents on reversal of reserpine-induced impairment in conditioned avoidance response in rats
    T Nakagawa
    Central Research Institute, Kaken Pharmaceutical Co Ltd, Kyoto, Japan
    Pharmacol Biochem Behav 58:829-36. 1997
    ..These results suggest that the DAergic nervous system rather than the adrenergic or 5-HT nervous system is involved in RII in CAR, and that both the DAergic D1- and D2-mediated nervous systems play important roles in this process...
  20. ncbi Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management
    J M Senard
    Laboratory of Medical and Clinical Pharmacology, INSERM U317, Faculty of Medicine, Paul Sabatier University, Toulouse, France
    Drugs Aging 18:495-505. 2001
    ..There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations...
  21. pmc Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine
    Michael T Heneka
    Department of Neurology, Deutsches Zentrum für Neurodegenerative Erkrankungen, University of Bonn, 53105 Bonn, Germany
    Proc Natl Acad Sci U S A 107:6058-63. 2010
    ..Consequently, therapies targeting microglial phagocytosis should be tested under NE depletion...
  22. ncbi The Movement Disorder Society--14th International Congress of Parkinson's Disease and Movement Disorders
    Donald Grosset
    Southern General Hospital, Department of Neurology, Institute of Neurological Sciences, Glasgow, UK
    IDrugs 13:539-42. 2010
    ..on drug treatments for movement disorders, including safinamide (Merck Serono SA), PYM-50028 (Phytopharm plc), droxidopa, pardoprunox (Abbott Laboratories); treatment considerations for dystonia; exploiting existing drugs for new ..
  23. ncbi Tyrosine hydroxylase and aromatic L-amino acid decarboxylase do not coexist in neurons in the human anterior cingulate cortex
    K Ikemoto
    Department of Anatomy, Fujita Heath University, School of Medicine, Toyoake, Japan
    Neurosci Lett 269:37-40. 1999
    ..AADC neurons in the human ACC might transform L-DOPA to dopamine, droxidopa to noradrenaline, and/or 5-hydroxytryptophan to serotonin.
  24. ncbi Total norepinephrine spillover, muscle sympathetic nerve activity and heart-rate spectral analysis in a patient with dopamine beta-hydroxylase deficiency
    J M Thompson
    Alfred Baker Medical Unit, Alfred Hospital, Victoria, Australia
    J Auton Nerv Syst 55:198-206. 1995
    ....
  25. ncbi Central nervous stimulants facilitate sexual behavior in male rats with medial prefrontal cortex lesions
    A Agmo
    Department of Psychology, Universidad Anahuac, Mexico City, Mexico
    Brain Res 696:187-93. 1995
    ..Noradrenergic stimulation cannot, therefore, be important for the effects of amphetamine or amfonelic acid...
  26. ncbi The effects of L-threo-3,4-dihydroxyphenylserine on the total norepinephrine and dopamine concentrations in the cerebrospinal fluid and freezing gait in parkinsonian patients
    H Tohgi
    Department of Neurology, Iwate Medical University, Morioka, Japan
    J Neural Transm Park Dis Dement Sect 5:27-34. 1993
    ..These results indicate that L-DOPS administration increases the NE concentration dose-dependently, and is effective for freezing of gait of moderate severity...
  27. ncbi L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug
    David S Goldstein
    Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA
    Cardiovasc Drug Rev 24:189-203. 2006
    ..L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension...
  28. ncbi Recent advances in pharmacological therapy of Parkinson's disease
    P Riederer
    Department of Clinical Neurochemistry, University Hospital for Nervous Diseases, Wurzburg, Germany
    Adv Neurol 60:626-35. 1993
    ..Possible neuroprotective strategies include selective MAO-B inhibitors, iron chelators, and free radical scavengers...
  29. ncbi The protective effect of L-threo-3,4-dihydroxyphenylserine on ischemic hippocampal neuronal death in gerbils
    T H Lee
    Department of Neurology, Tohoku University School of Medicine, Sendai, Japan
    Stroke 25:1425-31; discussion 1432. 1994
    ..We evaluated the possible protective effect of DOPS against hippocampal CA1 cell death after transient forebrain ischemia in gerbils...
  30. ncbi [Development of L-threo-DOPS, a norepinephrine precursor amino acid]
    J Katsube
    Sumitomo Pharmaceuticals Co, Ltd, Osaka, Japan
    Yakugaku Zasshi 114:823-46. 1994
    ..The R & D of L-DOPS described in this paper includes studies on industrial production, efficacy pharmacology (mode of action), metabolism and clinical trial of this agent...
  31. ncbi Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa
    J Kurihara
    Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan
    Biol Pharm Bull 23:1445-9. 2000
    ..was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.)...
  32. ncbi An L-DOPA-like depressor action of L-threo-dihydroxyphenyl-serine in the rat caudal ventrolateral medulla
    N Furukawa
    Department of Pharmacology, Yokohama City University School of Medicine, Yokohama, Japan
    Life Sci 61:1177-83. 1997
    ..001-100 ng), which contrasted with the cardiopressor action of L-DOPA applied in RVLM. In RVLM, there may exist an L-threo-DOPS-insensitive recognition site for L-DOPA...
  33. ncbi Improved cardiac iodine-123 metaiodobenzylguanidine accumulation after drug therapy in a patient with Parkinson's disease
    N Kanzaki
    Department of Radiology, National Minami Okayama Hospital, Japan
    Clin Nucl Med 22:697-9. 1997
    ..Cardiac I-123 MIBG imaging may be a promising new method for evaluating drug therapy in patients with Parkinson's disease...
  34. ncbi Impaired maternal behavior in mice lacking norepinephrine and epinephrine
    S A Thomas
    Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle 98195, USA
    Cell 91:583-92. 1997
    ..Our results suggest that NE is responsible for long-lasting changes that promote maternal behavior during both development and parturition in mice...
  35. ncbi Optimal production of L-threo-2,3-dihydroxyphenylserine (L-threo-DOPS) on a large scale by diastereoselectivity-enhanced variant of L-threonine aldolase expressed in Escherichia coli
    Hui Jeong Gwon
    Department of Food Science and Human Nutrition, and Research Institute of Human Ecology, Chonbuk National University, Jeonju, Jeonbuk, Korea
    Prep Biochem Biotechnol 42:143-54. 2012
    ..2%. Our results indicate this potential procedure as an economical purification process for the synthesis and purification of important L-threo-DOPS at the pharmaceutical level...
  36. ncbi L-threo-3,4-dihydroxyphenylserine enhances the orthostatic responses of plasma renin activity and angiotensin II in multiple system atrophy
    T Yoshizawa
    Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Japan
    J Neurol 246:193-7. 1999
    ..The enhanced responses of these vasoactive mediators by L-threo-DOPS during head-up tilt may contribute to the improvement in orthostatic hypotension in patients with MSA...
  37. ncbi The treatment of neurogenic orthostatic hypotension with 3,4-DL-threo-dihydroxyphenylserine: a randomized, placebo-controlled, crossover trial
    R Freeman
    Department of Neurology, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA 02215, USA
    Neurology 53:2151-7. 1999
    ..To study the therapeutic effect and mechanism of action of 3,4-DL-threodihydroxyphenylserine (DL-DOPS) in neurogenic orthostatic hypotension...
  38. ncbi Synthesis of 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl)serine as potential in vivo precursors of fluorinated norepinephrines
    B Herbert
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Org Chem 66:4892-7. 2001
    ..Removal of the chiral auxiliary and blocking groups produced the target amino acids 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl)serine (1b and 1c) in >98% ee...
  39. ncbi Contamination of the norepinephrine prodrug droxidopa by dihydroxyphenylacetaldehyde
    Courtney Holmes
    Clinical Neurocardiology Section, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 1620, USA
    Clin Chem 56:832-8. 2010
    L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxidopa) is a norepinephrine (NE) prodrug under development to treat orthostatic hypotension...
  40. ncbi Structural optimization of SadA, an Fe(II)- and α-ketoglutarate-dependent dioxygenase targeting biocatalytic synthesis of N-succinyl-L-threo-3,4-dimethoxyphenylserine
    Hui min Qin
    Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
    Biochem Biophys Res Commun 450:1458-61. 2014
    L-threo-3,4-Dihydroxyphenylserine (l-DOPS, Droxidopa) is a psychoactive drug and synthetic amino acid precursor that acts as a prodrug to the neurotransmitters...
  41. ncbi Outflow of dopamine and noradrenaline originating from L-dopa and L-threo-DOPS in rat renal tissues
    M Pestana
    Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal
    Gen Pharmacol 25:879-85. 1994
    ..The administration of L-DOPS was also found to be accompanied by the accumulation in renal tissues of DOPEG; this was, however, not dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS)..
  42. ncbi Determination of D,L-threo-3,4-dihydroxyphenylserine and of the D- and L-enantiomers in human plasma and urine
    F Boomsma
    Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands
    J Chromatogr 427:219-27. 1988
    ..28; r = 0.997; n = 52). Excellent agreement was found between the sum of the D- and L-DOPS concentrations and the measured total D,L-DOPS concentration (regression line DOPS (D + L) = 0.955 DOPS (total, LE) + 116.65; r = 0.992; n = 100)...
  43. ncbi Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation
    D Robertson
    Department of Pharmacology, Vanderbilt University, Nashville, Tenn 37232 2195
    Hypertension 18:1-8. 1991
    ..Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one...
  44. ncbi Effects of L-threo-DOPS, a noradrenaline precursor, on the long-term potentiation in the rat hippocampal mossy fiber-CA3 region
    N Sakai
    Department of Pharmacology, Kobe University School of Medicine, Japan
    Brain Res 567:267-73. 1991
    ..These results suggest that NE converted from L-threo-DOPS plays an important role in inducing LTP in the mossy fiber-CA3 system in the animals deficient in catecholamines...
  45. ncbi [Inhibitory effects of L-threo-DOPS on electroshock seizure in mice]
    M Yoshida
    Department of Neurology, University of Tsukuba, Ibaraki, Japan
    No To Shinkei 41:567-73. 1989
    ..It was suggested that L-DOPS would be a useful substance for the investigation on a role of NE in experimental epilepsy and could be used clinically as an adjunct drug for generalized tonic-clonic convulsions...
  46. ncbi Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activities in Shy-Drager syndrome
    T Kachi
    Department of Neurology, National Chubu Hospital, Obu, Japan
    Neurology 38:1091-4. 1988
    ..We suggest that the OH improved mainly because of the increase in MSA due to L-threo-DOPS, and that the drug may activate sympathetic outflow at a site proximal to the sympathetic ganglion...
  47. pmc Shy-Drager syndrome. Effect of fludrocortisone and L-threo-3,4-dihydroxyphenylserine on the blood pressure and regional cerebral blood flow
    S Matsubara
    Department of Neurology, Kanazawa University School of Medicine, Japan
    J Neurol Neurosurg Psychiatry 53:994-7. 1990
    ..Fludrocortisone reduced the fall of the mean blood pressure significantly. DOPS reduced the fall of both the diastolic blood pressure and rCBF significantly...
  48. ncbi Effects of biogenic amine precursors on ovarian steroid-induced LH release in acutely ovariectomized rats
    W P Pi
    Department of Physiology, College of Medicine, National Taiwan University, Taipei, R O C
    Chin J Physiol 33:335-43. 1990
    ..Results imply that the classical neurotransmitters in the central nervous system might modify the threshold of LHRH neurons in the hypothalamus...
  49. ncbi Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine beta hydroxylase
    C J Mathias
    Department of Medicine, St Mary s Hospital, London
    Q J Med 75:617-33. 1990
    ..The laevo isomer also raised blood pressure and plasma noradrenaline levels. The drug had no direct pressor effects, as its actions were prevented by the dopa-decarboxylase inhibitor, carbidopa...
  50. ncbi [Metrizamide encephalopathy in a child with hydrocephalus--effects of L-threo-DOPS on persistent disturbance of consciousness and L-dopa on extrapyramidal symptoms]
    S Usui
    Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
    No To Shinkei 40:1075-80. 1988
    ....
  51. ncbi Effects of L-threo- and erythro-3,4-dihydroxyphenylserine on learning performance and concentrations of brain noradrenaline and its metabolites in rats
    H Harada
    Department of Neuropsychiatry, Kyoto Prefectural University of Medicine, Japan
    Pharmacol Biochem Behav 43:215-21. 1992
    ..On the other hand, an intraventricular injection of 5 micrograms L-erythro-DOPS (the r-NA precursor) attenuated the learning performance, and this effect was probably caused by the formed r-NA from L-erythro-DOPS...
  52. ncbi Treatment of dialysis-induced hypotension with L-threo-3,4-dihydroxyphenylserine
    N Iida
    Department of Nephrology, Osaka Prefectural Hospital, Japan
    Nephrol Dial Transplant 9:1130-5. 1994
    ..L-DOPS appeared to be an effective and well-tolerated treatment for the prevention of dialysis-induced hypotension...
  53. ncbi d,l-threo-3,4-dihydroxyphenylserine restores sympathetic control and cures orthostatic hypotension in dopamine beta-hydroxylase deficiency
    A J Man in 't Veld
    Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands
    J Hypertens Suppl 6:S547-9. 1988
    ..Acting as an alternative substrate for ALAAD in the production of noradrenaline, DOPS is taken up by the neuron, restoring sympathetic control and thereby curing the orthostatic hypotension in DBH deficiency...
  54. ncbi A pharmacological study of hibernation in rodents
    C P Lyman
    Concord Field Station, Harvard University, Bedford, MA 01730
    Gen Pharmacol 19:565-71. 1988
    ..6. Phenylephrine caused vasoconstriction, but did not result in arousal. 7. No drug increased the sensitivity to peripheral stimuli during hibernation...
  55. ncbi Endogenous restoration of noradrenaline by precursor therapy in dopamine-beta-hydroxylase deficiency
    I Biaggioni
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    Lancet 2:1170-2. 1987
    ..88, p less than 0.05). Urinary noradrenaline increased from undetectable levels to 338 and 511 micrograms/24 h. Standing time (a correlate of functional capacity) also increased significantly in both patients. No side-effects were noted...
  56. ncbi Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system
    K C Lim
    Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois, USA
    Nat Genet 25:209-12. 2000
    ..Thus we have shown that Gata3 has a role in the differentiation of multiple cell lineages during embryogenesis...
  57. ncbi [A case of progressive supranuclear palsy dramatically improved with L-threo-3,4-dihydroxyphenylserine]
    T Maruyama
    Department of Neurology, Rehabilitation Center Kakeyu Hospital
    Rinsho Shinkeigaku 32:606-11. 1992
    ..abstract truncated at 250 words)..
  58. ncbi Differential effect of L-threo-3,4-dihydroxyphenylserine in pure autonomic failure and multiple system atrophy with autonomic failure
    H Kaufmann
    Department of Neurology, Mount Sinai School of Medicine, City University of New York, New York
    J Neural Transm Park Dis Dement Sect 3:143-8. 1991
    ..These results suggest that the site of action of L-threo-dops is central and that its pressor effect requires intact peripheral sympathetic neurons...
  59. ncbi Medical treatment of freezing of gait
    Nir Giladi
    Movement Disorders Unit, Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Mov Disord 23:S482-8. 2008
    ....
  60. ncbi Emerging drugs for autonomic dysfunction in Parkinson's disease
    Santiago Perez-Lloret
    University of Toulouse III, University Hospital, Department of Clinical Pharmacology and Neuroscience, Toulouse, France
    Expert Opin Emerg Drugs 18:39-53. 2013
    ..Even though its treatment has been recognized as a major unmet need in PD, there is a paucity of clinical trials to assess their treatment...
  61. ncbi Hemodynamic effects of L-threo-3,4-dihydroxyphenylserine (Droxidopa) in hypotensive individuals with spinal cord injury
    Jill M Wecht
    Center of Excellence, James J Peters Veterans Affairs Medical Center, Bronx, NY Medical Service, James J Peters Veterans Affairs Medical Center, Bronx, NY Department of Medicine, The Mount Sinai School of Medicine, New York, NY Department of Rehabilitation Medicine, The Mount Sinai School of Medicine, New York, NY Electronic address
    Arch Phys Med Rehabil 94:2006-12. 2013
    To determine the effect of an escalating dose of droxidopa (100, 200, and 400 mg) compared with placebo on seated blood pressure (BP) in hypotensive individuals with spinal cord injury (SCI)...
  62. ncbi Is there room for new non-dopaminergic treatments in Parkinson's disease?
    Manuela Pilleri
    Department for Parkinson s Disease, IRCCS San Camillo, via Alberoni 70, Venice, Italy
    J Neural Transm 120:349-52. 2013
    ....
  63. pmc L-threo-dihydroxyphenylserine corrects neurochemical abnormalities in a Menkes disease mouse model
    Anthony Donsante
    Unit on Human Copper Metabolism, Molecular Medicine Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD 20892 1853, USA
    Ann Neurol 73:259-65. 2013
    ....
  64. ncbi Embryonic lethality in mice lacking mismatch-specific thymine DNA glycosylase is partially prevented by DOPS, a precursor of noradrenaline
    Yusuke Saito
    Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai, Japan
    Tohoku J Exp Med 226:75-83. 2012
    ..5 dpc, suggesting that the lethality in (-/-) embryos is partially due to the reduction of noradrenaline. These results suggest that embryonic lethality in Tdg (-/-) embryos is due, in part, to the reduction of noradrenaline levels...
  65. pmc The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer's disease
    Sergey Kalinin
    Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA
    Neurobiol Aging 33:1651-63. 2012
    ..These data demonstrate the presence of LC stress in a robust mouse model of AD, and suggest that raising CNS NA levels could provide benefit in AD...
  66. ncbi [Localization of non-monoaminergic aromatic L-amino acid decarboxylase neurons (D-neurons) in the human striatum and their functional significance]
    Keiko Ikemoto
    Clinical Research Institute, National Minami Hanamaki Hospital, 500 Suwa, Hanamaki, Iwate 025 0033, Japan
    Kaibogaku Zasshi 77:71-5. 2002
    ..of efficacy of pharmacotherapy for Parkinson's disease by uptaking monoamine precursors including L-dopa or droxidopa (L-threo-DOPS) and by converting them to dopamine or noradrenaline, respectively...
  67. pmc Pure akinesia: an atypical manifestation of progressive supranuclear palsy
    H Matsuo
    First Department of Internal Medicine, Nagasaki University, School of Medicine, Japan
    J Neurol Neurosurg Psychiatry 54:397-400. 1991
    ..At necropsy, pathological findings were not different from those reported for PSP. It is suggested that "pure akinesia" is an atypical manifestation of PSP, and that norepinephrinergic neurons may be involved in some types of PSP...
  68. ncbi Diuretic effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) in anesthetized rats
    S Morimoto
    Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan
    Jpn J Pharmacol 52:431-9. 1990
    ..These results indicate that diuresis and natriuresis induced by L-threo-DOPS are dependent on the pressor effect of NE via peripheral alpha-adrenoceptor activation...
  69. ncbi [Analysis of L-threo-3, 4-dihydroxyphenylserine effect on motor and psychological symptoms in Parkinson's disease]
    H Narabayashi
    Neurological Clinic, Tokyo, Japan
    No To Shinkei 43:263-8. 1991
    ..Importance of the role of aging of the brain in each individual patient is discussed and interpreted in relation to the difference of clinical pictures...
  70. ncbi Sleeping with and without norepinephrine: effects of metoclopramide and D,L-threo-3,4-dihydroxyphenylserine on sleep in dopamine beta-hydroxylase deficiency
    J H Tulen
    Department of Psychiatry, University Hospital Dijkzigt, Rotterdam, The Netherlands
    Sleep 14:32-8. 1991
    ..These data indicate that in patients with DBH deficiency norepinephrine is not essential for the development of a normal sleep/wake pattern but may have a facilitatory role in the generation of REM sleep...
  71. ncbi L-threodops increases extracellular norepinephrine levels in the brain: an in vivo study
    T Brannan
    Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029
    Neurology 40:1134-5. 1990
    ..When peripheral decarboxylase activity was inhibited with carbidopa, administration of the same dose of L-threodops induced a 2.5-fold greater increase in norepinephrine levels...
  72. ncbi Role of noradrenergic signaling by the nucleus tractus solitarius in mediating opiate reward
    Valerie G Olson
    Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Science 311:1017-20. 2006
    ..Morphine-induced locomotion was partially restored by DBH expression in either brain region. These data suggest that NE signaling by the nucleus tractus solitarius is necessary for morphine reward...
  73. pmc A requirement for memory retrieval during and after long-term extinction learning
    Ming Ouyang
    Department of Pharmacology, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, USA
    Proc Natl Acad Sci U S A 102:9347-52. 2005
    ..In addition, the timing over which extinction is sensitive to adrenergic manipulation suggests a model whereby memory retrieval occurs during, and several hours after, extinction learning to consolidate long-term extinction memory...
  74. ncbi Noradrenaline is necessary for the hedonic properties of addictive drugs
    Luc Jasmin
    Department of Neurological Surgery and W M Keck Foundation Center for Integrative Neuroscience, University of California San Francisco, San Francisco, CA 94143, USA
    Vascul Pharmacol 45:243-50. 2006
    ..The reversibility of this phenomenon, by restoring NA, indicates that even when this behavioral deficit is genetically determined it can be reversed...
  75. ncbi A case of syndrome of inappropriate secretion of antidiuretic hormone associated with diabetes mellitus
    K Sato
    Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan
    Endocrinol Jpn 38:331-8. 1991
    ..After treatment with droxidopa "a sympathomimetic drug", ambulatory blood pressure gradually increased and hyponatremia disappeared...
  76. pmc Noradrenergic control of cortico-striato-thalamic and mesolimbic cross-structural synchrony
    Kafui Dzirasa
    Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Neurosci 30:6387-97. 2010
    ....
  77. ncbi [New perspectives on molecular and genic therapies in Down syndrome]
    Jean Maurice Delabar
    Unité de Biologie Fonctionnelle et Adaptative BFA, EAC CNRS 4413, Universite Paris Diderot, Marie Andrée Lagroua Weill Hallé, Batiment Lamarck, 75205 Paris, France
    Med Sci (Paris) 26:371-6. 2010
    ..It is promising that strategies targeting specific genes or specific pathways are already giving positive results...
  78. ncbi Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activity in humans
    S Iwase
    Department of Autonomic and Behavioral Neurosciences, Nagoya University, Japan
    J Auton Nerv Syst 39:159-67. 1992
    ....
  79. ncbi Activation of an adrenergic pro-drug through sequential stereoselective action of tandem target enzymes
    J Debnath
    School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta 30332
    Biochem Biophys Res Commun 189:33-9. 1992
    ..These results provide a heretofore unrecognized rationale for the bioactivity of L-erythro DOPS and provide a basis for the design of new adrenergic pro-drugs...
  80. ncbi Treatment of dysautonomia associated with Parkinson's disease
    Giovanni Mostile
    Parkinson s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA
    Parkinsonism Relat Disord 15:S224-32. 2009
    ..Orthostatic hypotension: fludrocortisone, midodrine, and droxidopa; 2. Sialorrhea: glycopyrrolate and botulinun toxin injections; 3...
  81. ncbi L-threo-3,4-dihydroxyphenylserine enhanced ocular dominance plasticity in adult cats
    N Mataga
    Department of Neuroscience, Osaka Bioscience Institute, Japan
    Neurosci Lett 142:115-8. 1992
    ..These results suggest that peripheral administration of L-threo-DOPS enhances ocular dominance plasticity, presumably through activation of the central noradrenergic system...
  82. ncbi Diastereoselective synthesis of L: -threo-3,4-dihydroxyphenylserine by low-specific L: -threonine aldolase mutants
    Hui Jeong Gwon
    Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 1266 Jeongeup, Jeonbuk, 580 185, Republic of Korea
    Biotechnol Lett 32:143-9. 2010
    ..When aldol condensation activity was examined using whole cells of T3-3mm2, its de was constantly maintained at 55% during the batch reactions for 80 h, yielding 3.8 mg L: -threo-DOPS/ml...
  83. ncbi Enhanced synthesis of L-threo-3,4-dihydroxyphenylserine by high-density whole-cell biocatalyst of recombinant L-threonine aldolase from Streptomyces avelmitilis
    Sang Ho Baik
    Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, Jeonbuk, 561 756, South Korea
    Biotechnol Lett 31:443-8. 2009
    ..75% Triton-X, 5 g E. coli cells/l, pH 6.5 and 10 degrees C. In the optimized condition, overall productivity was 8 g/l, which represents 40 times the synthesis yield possible with no optimization of conditions...
  84. pmc Alpha2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment
    Sudhirkumar U Yanpallewar
    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India
    J Neurosci 30:1096-109. 2010
    ....
  85. ncbi [A case of "pure" progressive autonomic failure in an elderly male]
    T Kuwahara
    Second Department of Internal Medicine, Ehime University School of Medicine
    Nihon Ronen Igakkai Zasshi 29:790-3. 1992
    ..It shows symptoms of autonomic failure without other neurological disturbances which manifest as Shy-Drager syndrome. Treatment with L-DOPS increased his blood pressure level and attenuated his symptoms due to orthostatic hypotension...
  86. ncbi Effect of L-threo-3, 4-dihydroxyphenylserine on orthostatic hypotension in a patient with spinal cord injury
    S Muneta
    Second Department of Internal Medicine, Ehime University School of Medicine, Japan
    Jpn Circ J 56:243-7. 1992
    ..Treatment of the patient with salt supplement and L-threo-3, 4-dihydroxyphenylserine, an exogenous precursor of norepinephrine, markedly improved the syncopal attack as well as the daily activity...
  87. ncbi Effect of long-term L-threo-3,4-dihydroxyphenylserine administration on alpha 2-adrenergic receptors in platelet membranes in neurologic disorders
    T Azuma
    Center for Adult Disease, Osaka, Japan
    Acta Neurol Scand 84:46-50. 1991
    ....
  88. ncbi Synthesis of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) with thermostabilized low-specific L-threonine aldolase from Streptomyces coelicolor A3(2)
    Sang Ho Balk
    NITE Biological Resource Center, National Institute of Technology and Evaluation, 2 5 8 Kazusa kamatari, Kisarazu shi, Chiba 292 0818, Japan
    J Microbiol Biotechnol 17:721-7. 2007
    ..0 mg/ml of L-threo-DOPS. This result showed that H44 L-TA is more effective than the wild-type L-TA for the mass production of L-threo-DOPS...
  89. ncbi Midodrine hydrochloride and L-threo-3,4-dihydroxy-phenylserine preserve cerebral blood flow in hemodialysis patients with orthostatic hypotension
    Kiichiro Fujisaki
    Department of Medicine and Clinical Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
    Ther Apher Dial 11:49-55. 2007
    ..Although MID and L-DOPS did not prevent OH after HD in HD patients, both agents preserved cerebral blood flow during orthostasis in HD patients with OH...
  90. ncbi DBH deficiency in an elderly patient: efficacy and safety of chronic droxidopa
    Fabien Despas
    INSERM U858 équipe 8, 31432 Toulouse, France
    Clin Auton Res 20:205-7. 2010
    We describe the effects of chronic droxidopa in a patient with Dopamine beta-hydroxylase deficiency diagnosed at the age of 73...
  91. ncbi Significance of human striatal D-neurons: implications in neuropsychiatric functions
    Keiko Ikemoto
    Clinical Research Institute, National Minami Hanamaki Hospital, 500 Suwa, Hanamaki, Iwate, 025 0033, Japan
    Prog Neuropsychopharmacol Biol Psychiatry 28:429-34. 2004
    ..of efficacy of pharmacotherapy for Parkinson's disease by taking up monoamine precursors including L-dopa or droxidopa (L-threo-DOPS) and by converting them to dopamine or noradrenaline, respectively...
  92. ncbi Amine precursor amino acid therapy: from neurochemical basis to clinical aspects
    T Nakajima
    Department of Neuropsychiatry, Kyoto Perfectural University of Medicine, Kawaramachi Hirokoji, Kamigyoku, Kyoto, Japan
    Neurochem Res 21:251-8. 1996
    ..Furthermore, peculiar or artificial amino acids which are metabolized into the brain amine or their derivatives and promised their clinical application are also introduced...
  93. ncbi [The effect of droxidopa on the monoamine metabolsim in the human brain]
    W Maruyama
    Department of Neurology, Nagoya University School of Medicine
    Rinsho Shinkeigaku 34:985-90. 1994
    b>Droxidopa (L-threo-3,4-dihydroxyphenylserine) is an artificial amino acid, which is used to supplement noradrenaline (NA) in neurodegenerative disorders...
  94. ncbi The treatment of postprandial hypotension in autonomic failure with 3,4-DL-threo-dihydroxyphenylserine
    R Freeman
    Department of Neurology, Beth Israel Deaconess Medical Center, Hebrew Rehabilitation Center for the Aged, Boston, MA, USA
    Neurology 47:1414-20. 1996
    ....
  95. ncbi The effects of the noradrenaline precursor, L-threo-3,4-dihydroxyphenylserine, in children with orthostatic intolerance
    H Tanaka
    Department of Pediatrics, Osaka Medical College, Japan
    Clin Auton Res 6:189-93. 1996
    ..There were no adverse effects reported. These preliminary studies have indicated that L-DOPS may be an effective drug for the treatment of orthostatic intolerance in children...
  96. ncbi The metabolism of L-DOPA and L-threo-3,4-dihydroxyphenylserine and their effects on monoamines in the human brain: analysis of the intraventricular fluid from parkinsonian patients
    W Maruyama
    Department of Neurology, Nagoya University School of Medicine, Japan
    J Neurol Sci 139:141-8. 1996
    ..An overview of the metabolism of neurotransmitters in the brain proved to be useful to evaluate the therapeutic effects of these precursor amino acids...
  97. ncbi Effect of monoamine precursors on the forced-swimming test in mice
    J I Semba
    Department of Neuropsychiatry, Faculty of Medicine, Tokyo Medical and Dental University, Japan
    Psychopharmacology (Berl) 95:222-5. 1988
    ..These results suggest possible antidepressant properties of DOPA and DOPS, the latter of which may act as an antidepressant in a certain NE-depleting condition...
  98. ncbi The role of L-threo DOPS in the control of Na-K ATPase activity of the marginal cells in the stria vascularis of reserpinized guinea pigs
    N Kanoh
    Department of Otolaryngology, Hyogo College of Medicine, Japan
    Acta Otolaryngol Suppl 520:381-3. 1995
    ..These results suggest that catecholamines may play an essential role in the maintenance or control of the Na-K ATPase activity, and that the stria vascularis may be one of the target organs of catecholamines...
  99. pmc Acute pandysautonomia: mass spectrometric and histopathological studies of the sympathetic nervous system during long term L-threo-3,4-dihydroxyphenylserine treatment
    M Ushiyama
    Department of Neurology, Kenwakai Hospital, Iida, Japan
    J Neurol Neurosurg Psychiatry 61:99-102. 1996
    ..Noradrenergic nerve fibres in the rectal mucosa showed no recovery, and so clinical improvement had occurred without apparent significant regeneration of the peripheral autonomic nerves...
  100. ncbi A new metabolic pathway of L-threo-3,4-dihydroxyphenylserine, a precursor amino acid of norepinephrine, in the brain. Studies by in vivo microdialysis
    W Maruyama
    Department of Neurology, Nagoya University School of Medicine, Japan
    J Neural Transm Park Dis Dement Sect 7:21-33. 1994
    ..Inhibition of DOPS-aldolase should improve its effectiveness as the supplement therapy of norepinephrine...
  101. ncbi Studies of neurocirculatory effects of long-term L-threo-3,4-dihydroxyphenylserine administration in a patient with familial amyloidotic polyneuropathy
    T Azuma
    Third Department of Internal Medicine, Osaka University Hospital, Japan
    Acta Neurol Scand 77:409-13. 1988
    ..Testing of autonomic function under telemetric intra-arterial pressure monitoring before and during L-threo-DOPS treatment clearly demonstrated the pathophysiology of the sympathetic nervous system and its modification by L-threo-DOPS...

Research Grants6

  1. PHARMACOLOGIC PROBES IN NEURALLY-MEDIATED SYNCOPE
    Italo Biaggioni; Fiscal Year: 2003
    ..These studies will be directly applicable to the evaluation and treatment of patients with these incapacitating disorders. ..
  2. Adenosine and Nitric Oxide Deficiency
    Italo Biaggioni; Fiscal Year: 2004
    ....
  3. Autonomic Nervous System in Chronic Fatigue Syndrome
    Italo Biaggioni; Fiscal Year: 2009
    ....
  4. OTOLITH INFLUENCES ON SYMPATHETIC ACTIVITY
    Horacio Kaufmann; Fiscal Year: 2004
    ..abstract_text> ..
  5. Carbidopa for the treatment of nausea and vomiting in familial dysautonomiaIND #
    Horacio Kaufmann; Fiscal Year: 2010
    ..Their long-term goal is to treat nausea effectively and without side effects, a therapeutic intervention that will markedly improve the quality of life of patients with FD. ..