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Remoxipride is a substituted benzamide that acts as a weak but very selective antagonist of dopamine D2 receptors. It was introduced by Astra (Roxiam) at the end of the eighties and was prescribed as an atypical antipsychotic. This article reviews its putative selective effects on mesolimbic versus nigrostriatal dopaminergic systems. In animals, remoxipride has minimal cataleptic effects at doses that block dopamine agonist-induced hyperactivity. These findings are predictive of antipsychotic activity with a low likelihood of extrapyramidal symptoms. Remoxipride also appears to be effective in more recent animal models of schizophrenia, such as latent inhibition or prepulse inhibition. In clinical studies, remoxipride shows a relatively low incidence of extrapyramidal side effects and its effects on prolactin release are short-lasting and generally mild. The clinical efficacy of remoxipride is similar to that of haloperidol or chlorpromazine. Although its clinical use was severely restricted in 1993, due to reports of aplastic anemia in some patients receiving remoxipride, this drug has been found to exhibit relatively high selectivity for dopamine D2 receptors making remoxipride an interesting tool for neurochemical and behavioral studies.

Phenothiazines are widely used in older patients, but little experimental work has been carried out in this age group. Two groups of healthy volunteers, a younger group (Y: six males and six females, aged 20-42 years) and an older group (O: six males and eight females, aged 65-77 years) took part in a randomized double-blind three-period crossover study in which they received by mouth single doses of thioridazine (Y: 50 mg; O: 25 mg) remoxipride (Y: 100 mg; O: 50 mg) or placebo. Measures of central nervous system (CNS) and haemodynamic function were carried out before drug administration and at 1.5-h intervals up to 9 h post-dose, and blood samples were collected over a 24-h period. No significant differences in dose-corrected pharmacokinetic variables were found between the two groups. There was evidence of marked CNS depressant effects of thioridazine from both objective and subjective measures. The effects for remoxipride were similar, though generally less marked. After allowance was made for dose, there was little indication of any difference in degree of CNS depression between the two age groups. Haemodynamic measures showed orthostatic reductions in blood pressure with thioridazine which were particularly marked in the older group, who also showed lower compensatory increases in pulse rate. These results indicate potential problems with orthostatic hypotension with thioridazine in older patients. CNS depression may also be a problem, especially in patients with compromised cholinergic function.

The disposition of remoxipride was evaluated in 13 male chronic schizophrenic patients. A single 150 mg dose of remoxipride was administered and blood sampling performed over the following 48 hours. The mean (SD) oral clearance and half-life of remoxipride were 74.46 (25.9) ml/min and 5.46 (0.87) hours, respectively. The mean (SD) AUC for remoxipride was 25,320 (9,820) ng.h/ml. A wide interpatient variability was observed. Compared to Caucasian studies there were no significant differences in the disposition of remoxipride.

Clozapine, risperidone and remoxipride are three neuroleptics that represent an interesting alternative in the psychopharmacological treatment of schizophrenia. Pharmacodynamic and pharmacokinetic properties, efficacy, dosages as well as the indication of these three substances are studied. In certain particular situations, a complementary treatment is of important therapeutic use, the addition of benzodiazepines, lithium, carbamazepine or beta-blockers are discussed.