Sulpiride is a substituted
benzamide with a selective action on receptors of the
dopamine D2-like family, and clinical and pharmacological data suggest that it could be considered to be an atypical
antipsychotic.
Sulpiride penetrates the blood-brain barrier poorly because of its low
lipid solubility. It is mainly excreted unchanged in the urine, and accumulation of the
drug could occur in patients with renal dysfunction and possibly in elderly patients with declining glomerular filtration rate. At low dosages (50 to 150 mg/day),
sulpiride produces a disinhibiting and
antidepressant effect, which is probably related to its action on D2 presynaptic
autoreceptors, thus facilitating dopaminergic neurotransmission. Data have confirmed the efficacy of
sulpiride in patients with acute or chronic
schizophrenia during both short and long term treatment, but long term, placebo-controlled trials are still lacking. It is still doubtful whether
sulpiride is more effective than typical
antipsychotics for the treatment of negative symptoms. Data from clinical studies are controversial; the majority of authors indicate that
sulpiride produces a better recovery rate from negative than from positive symptoms at low doses, but it shows a similar efficacy either on negative and positive symptoms at higher doses. The safety profile of
sulpiride is similar to that of typical
antipsychotics, although the frequency of adverse effects seems to be globally lower. Extrapyramidal reactions appear generally to be mild.
Autonomic effects occur less frequently with
sulpiride than with typical
antipsychotics, showing no clinically relevant influence on cardiovascular parameters and, on the whole, good tolerability in elderly patients.
Sulpiride is known to induce
prolactin elevation in both serum and CSF, which may be associated with
impotence in men and diminished gonadal function in women; these effects appear to be dosage-dependent.
Sulpiride can be considered to be an atypical
antipsychotic, considering its action on negative, defective symptoms, its partial activity against positive symptoms, and its low incidence of extrapyramidal adverse effects.
Sulpiride could find its specific therapeutic role in elderly patients with
schizophrenia, as it shows a good margin of safety between therapeutic dosages and toxic concentrations.