Dopamine agonist treatment of schizophrenia with N-propylnorapomorphine

We administered N-propylnorapomorphine, a potent aporphine-family dopamine (DA) agonist, to schizophrenic patients with active psychotic symptoms. After acute administration a significant antipsychotic action of N-propylnorapomorphine, maximal at an oral dose of 19 mg, was noted. The antipsychotic action predominated in subjects with neuroleptic-responsive symptoms, not in neuroleptic-nonresponders. However, when N-propylnorapomorphine was administered on a subchronic dosage schedule, no antipsychotic effect occurred. These observations suggest a rapid-onset tolerance phenomenon of psychosis to N-propylnorapomorphine and are consistent with results from preclinical experiments. These data support the idea that the acute antipsychotic response of DA agonists is mediated by the DA autoreceptor but fail to provide evidence for the potential clinical usefulness of this treatment approach.