RMI-81,582, a novel antipsychotic drug

RMI-81,582 (2-chloro-11-3-dimethylaminopropylidene morphanthridene), a potential antipsychotic agent, was administered to eight chronic and four acute male schizophrenics in an open label study. Ten of twelve patients improved, particularly those who were experiencing their first hospitalization, regardless of whether they met Research Diagnostic Criteria for acute or chronic schizophrenia. Significant improvement was noted on the Clinical Global Impressions and Brief Psychiatric Rating Scale. No extrapyramidal side effects were noted and other adverse reactions were few. Serum prolactin levels, a measure of antidopaminergic activity, were increased by low-moderate dosages of RMI-81,582 in seven of eleven patients. Four patients had no increase in serum prolactin with RMI-81,582. In six of the seven patients who developed increases in serum prolactin, prolactin levels returned to those characteristic of the placebo period as the dosage of RMI-81,582 was increased. With classical neuroleptics, serum prolactin levels increase as the dose increases up to approximately the equivalent of chlorpromazine 600 mg/day and then remain fairly constant. The pattern of serum prolactin response in both man and laboratory animals and the absence of extrapyramidal side effects suggest RMI-81,582 may have a clozapine-like action.