JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Perrault, Gh.
Right arrow Articles by Scatton, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Perrault, Gh.
Right arrow Articles by Scatton, B.

Vol. 280, Issue 1, 73-82, 1997

Psychopharmacological Profile of Amisulpride: An Antipsychotic Drug with Presynaptic D2/D3 Dopamine Receptor Antagonist Activity and Limbic Selectivity

Gh. Perrault, R. Depoortere, E. Morel, D. J. Sanger and B. Scatton

Synthélabo Recherche, CNS Research Department, Bagneux, France

Amisulpride, a benzamide derivative, is an antipsychotic drug with a pharmacological profile distinct from that of classical neuroleptics such as haloperidol and from that of another benzamide, remoxipride. In mice, amisulpride antagonized hypothermia induced by apomorphine, quinpirole or (±) 7-hydroxy-2-(di-n-propylamino)-tetralin, an effect involving D2/D3 receptors, at similar doses (ED50 ~ 2 mg/kg i.p.), which were much lower than doses that blocked apomorphine-induced climbing, an effect involving postsynaptic D2 and D1 receptor activation (ED50 = 21 mg/kg i.p.). Much higher doses (ED50 = 54 mg/kg i.p.) of amisulpride were needed to block grooming behavior observed after a short period in water, a D1 receptor-mediated behavior. In rats, amisulpride preferentially inhibited effects produced by low doses of apomorphine (hypomotility and yawning), related to stimulation of presynaptic D2/D3 dopamine autoreceptors (ED50 = 0.3 and 0.19 mg/kg i.p.). By contrast, amisulpride antagonized apomorphine-induced hypermotility, a postsynaptic dopamine receptor-mediated effect, at a much higher dose (ED50 = 30 mg/kg i.p.). Amisulpride (100 mg/kg i.p.) only partially inhibited apomorphine-induced stereotypies (gnawing) and had no effect on stereotypies induced by d-amphetamine. However, d-amphetamine-induced hyperactivity was antagonized by doses of amisulpride as low as 3 mg/kg i.p., which may indicate selectivity of this drug for limbic dopaminergic mechanisms. In addition, in contrast to haloperidol or remoxipride, which produced catalepsy at doses 2 or 3 times higher than those that antagonized stereotypies induced by apomorphine, amisulpride did not induce catalepsy up to a dose of 100 mg/kg i.p., which occupies 80% of striatal D2 receptors. This pharmacological profile of amisulpride, characterized by a preferential blockade of effects involving presynaptic mechanisms and limbic structures, may explain the clinical efficacy of this drug against both negative and positive symptoms of schizophrenia and its low propensity to produce extrapyramidal side effects.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 JNMHome page
C. la Fougere, E. Meisenzahl, G. Schmitt, J. Stauss, T. Frodl, K. Tatsch, K. Hahn, H.-J. Moller, and S. Dresel
D2 Receptor Occupancy During High- and Low-Dose Therapy with the Atypical Antipsychotic Amisulpride: A 123I-Iodobenzamide SPECT Study
J. Nucl. Med., June 1, 2005; 46(6): 1028 - 1033.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
G. Grunder, A. Carlsson, and D. F. Wong
Mechanism of New Antipsychotic Medications: Occupancy Is Not Just Antagonism
Arch Gen Psychiatry, October 1, 2003; 60(10): 974 - 977.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
S. Leucht, G. Pitschel-Walz, R. R. Engel, and W. Kissling
Amisulpride, an Unusual ""Atypical"" Antipsychotic: A Meta-Analysis of Randomized Controlled Trials
Am J Psychiatry, February 1, 2002; 159(2): 180 - 190.
[Abstract] [Full Text] [PDF]

Home page
 J PsychopharmacolHome page
E. Legangneux, J. McEwen, K. A. Wesnes, L. Bergougnan, N. Miget, M. Canal, C. L'Heritier, J. L. Pinquier, and P. Rosenzweig
The acute effects of amisulpride (50 mg and 200 mg) and haloperidol (2 mg) on cognitive function in healthy elderly volunteers
J Psychopharmacol, March 1, 2000; 14(2): 164 - 171.
[Abstract] [PDF]

Home page
 J PsychopharmacolHome page
M. Papp and J. Wieronska
Antidepressant-like activity of amisulpride in two animal models of depression
J Psychopharmacol, January 1, 2000; 14(1): 46 - 52.
[Abstract] [PDF]

Home page
 J PsychopharmacolHome page
L. Ravizza
Amisulpride in medium-term treatment of dysthymia: a six-month, double-blind safety study versus amitriptyline
J Psychopharmacol, May 1, 1999; 13(3): 248 - 254.
[Abstract] [PDF]

Home page
 Am. J. PsychiatryHome page
J.-M. Danion, W. Rein, O. Fleurot, and the Amisulpride Study Group
Improvement of Schizophrenic Patients With Primary Negative Symptoms Treated With Amisulpride
Am J Psychiatry, April 1, 1999; 156(4): 610 - 616.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. Di Giovanni, M. Di Mascio, V. Di Matteo, and E. Esposito
Effects of Acute and Repeated Administration of Amisulpride, a Dopamine D2/D3 Receptor Antagonist, on the Electrical Activity of Midbrain Dopaminergic Neurons
J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 51 - 57.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. Cohen, D. J. Sanger, and G. Perrault
Characterization of the Discriminative Stimulus Produced by the Dopamine Antagonist Tiapride
J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 566 - 573.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.