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The theoretical role of sigma receptors in psychosis has led to the development of selective sigma receptor ligands as potential antipsychotic agents. BMY 14802 has its most potent binding at the sigma binding site, with some degree of serotonin subtype 1A and negligible dopamine receptor binding. It is atypical of standard neuroleptics in that it does not induce catalepsy in rats. It has been shown to have efficacy in animal models of psychosis. It was hypothesized that the drug would have antipsychotic effects in humans without producing the extrapyramidal side effects typical of standard neuroleptics. We report here the results of an uncontrolled, multicenter safety and efficacy study of patients with acute exacerbations of schizophrenia treated with BMY 14802. After 1 week of single-blind placebo treatment, 28 patients were treated with BMY 14802 (up to 3000 mg/day) for up to 4 weeks. There was no significant improvement in psychiatric symptoms, as measured by the total Brief Psychiatric Rating Scale scores or Clinical Global Improvement. There were no changes in involuntary movements, as measured by the Abnormal Involuntary Movement Scale, or in extrapyramidal symptoms as measured by the Simpson-Angus Scale.

BMY 14802, a Sigma Receptor Ligand for the Treatment of Schizophrenia