Amisulpride is a benzamide derivative with a unique neurochemical and
pschopharmacological profile. This compound has selective affinity for
human dopamine D-3 and D-2 receptor subtypes in vitro (binding consta
nt, K-i similar to 3 nmol/l) and blocks functional responses mediated
by these receptors. In ex vivo binding studies, amisulpride is twice a
s selective for D, as for D, receptors. At low doses, it preferentiall
y blocks presynaptic dopamine autoreceptors (increase in dopamine rele
ase in vivo in the rat olfactory tubercle, 50% effective dose, ED50 3.
7 mg/kg), while postsynaptic dopamine receptor antagonism is apparent
at higher doses (decrease in striatal acetylcholine levels, ED(50)simi
lar to 60 mg/kg). Amisulpride preferentially stimulates dopamine synth
esis and displaces H-3-raclopride binding in vivo in the limbic system
rather than the striatum. It antagonizes apomorphine-induced hypother
mia in mice and amphetamine-induced hypermotility in rats at low doses
(ED50 2-3 mg/kg), blocks apomorphine-induced climbing and spontaneous
grooming in mice, blocks apomorphine-induced gnawing in rats at highe
r doses (ED50 19-115 mg/kg) and does not induce catalepsy at 100 mg/kg
. The preferential antagonism by amisulpride of presynaptic D,ID, rece
ptors is reflected behaviourally in the potent blockade of apomorphine
-induced effects mediated by dopamine autoreceptors (yawning and hypom
otility: ED50 0.2 and 0.3 mg/kg, respectively) compared with those med
iated by postsynaptic D-2 receptors (e.g, gnawing; ED50 115 mg/kg). Mo
reover, low doses of amisulpride induce prohedonic (potentiation of fo
od-induced place preference) effects in rats. The atypical neurochemic
al and psychopharmacological profiles of amisulpride may explain its t
herapeutic efficacy on both positive and negative symptoms of schizoph
renia.