A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers

Abstract

Amisulpride binds selectively to dopamine D(2) and D(3) receptors in the limbic system. Low doses of amisulpride preferentially block presynaptic D(2)/D(3)-dopamine autoreceptors, thereby enhancing dopaminergic transmission, whereas higher doses block postsynaptic receptors, thus inhibiting dopaminergic hyperactivity. Amisulpride is clinically effective on the negative symptoms of acute schizophrenia exacerbations at low dosages (50-300 mg/day), and also on the positive symptoms of the disease at high dosages (400-800 mg/day). Nineteen clinical studies involving 358 volunteers have investigated the pharmacokinetics, pharmacodynamics and tolerability of amisulpride. Amisulpride shows linear pharmacokinetics, a bioavailability of 48%, low protein binding (17%) and an elimination half-life of approximately 12 h. It is predominantly eliminated in the urine as the parent compound. It exhibits no significant detrimental effects in psychometric or memory tests up to the dose of 400 mg/day, inducing only mild impairment at high doses, whereas EEG data suggest an alertness-enhancing effect at low doses (<or= 50 mg). Moreover, amisulpride does not potentiate the depressant effects on the central nervous system of alcohol and lorazepam. This tolerability profile is clearly better than that of haloperidol 4 mg/day and is consistent with a weak blocking effect on striatal D(2) receptors. In summary, studies in humans have shown that amisulpride is free of behavioural toxicity at doses exerting clear antipsychotic efficacy and confirm that its CNS effects may vary with the dose administered.

Comparative evaluation of Amisulpride and Escitalopram on Hamilton Anxiety Rating Scale among depression patients in a tertiary care teaching hospital in Nepal

“…Gastrointestinal disturbances were seen most commonly with both the groups and have been proven in earlier studies. 35,36 Endocrinological effects like amenorrhea and lactation were seen in amisulpride group and have been seen in previous studies. 37 Other side effects such as insomnia, agitation and dryness of mouth were seen similarly in both groups and were comparable with previous studies.…”

The Poorly Membrane Permeable Antipsychotic Drugs Amisulpride and Sulpiride Are Substrates of the Organic Cation Transporters from the SLC22 Family

“…The maximal plasma concentrations after oral administration of 50 mg amisulpride or 100 mg sulpiride are 0.13 and 0.29 μM, respectively (48,49). These values are much lower than the K M for the uptake of amisulpride and sulpiride by the transporters studied ( Table I), meaning that transport in vivo will not be saturated.…”

“…The renal clearances of amisulpride and sulpiride are 330 and 223 ml/min, respectively (48,49) indicating that tubular secretion plays substantial role in their renal elimination. OCT2 is strongly expressed in proximal tubules (8), and it is probable that OCT2 is responsible for the significant tubular secretion of both drugs.…”

“…OCT1 is the major organic cation transporter in human hepatocytes (11,26). Amisulpride and sulpiride are not metabolized in the liver, but biliary excretion may account for up to 20% of their clearance (48,49). Hence, influx transport by SLC22 transporters in kidney and intestine (and potentially in liver) may be an important determinant of the plasma concentrations of both drugs.…”

Plasma amisulpride levels in schizophrenia or schizoaffective disorder

“…The amisulpride recovery from spiked samples was 79.8 F 2.2% and 81.9 F 2.5% at 50 and 400 ng/ml. The pharmacokinetics of the two enantiomers and the racemic mixture have been shown to differ for amisulpride, which is a chiral drug (Rosenzweig et al, 2002). The analytical method applied in the present study is an achiral procedure; thus, our data do not distinguish between the two enantiomers and represent plasma levels of the amisulpride racemate.…”