RT Journal Article
SR Electronic
T1 Psychopharmacological Profile of Amisulpride: An Antipsychotic Drug with Presynaptic D<sub>2</sub>/D<sub>3</sub> Dopamine  Receptor Antagonist Activity and Limbic Selectivity
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 73
OP 82
VO 280
IS 1
A1 Gh. Perrault
A1 R. Depoortere
A1 E. Morel
A1 D. J. Sanger
A1 B. Scatton
YR 1997
UL http://jpet.aspetjournals.org/content/280/1/73.abstract
AB 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 D1receptor-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. The American Society for Pharmacology and Experimental Therapeutics