Lack of apparent antipsychotic effect of the D1-dopamine recepotr antagonist SCH39166 in acutely ill schizophrenic patients

SCH 39166 is the first selective D1 dopamine receptor antagonist developed for the treatment of schizophrenic patients. To examine potential antipsychotic effect, tolerability and safety, SCH 39166 was given orally to 17 acutely ill drug free schizophrenic patients (DSMIIIR) in an open 4-week study. Doses were escalated from 10 to 100 mg b.i.d. according to a fixed schedule over 17 days and remained at 100 mg b.i.d. for another 11 days. The drug was withdrawn prematurely in ten patients because of deterioration or refusal to take SCH 39166. In the nine patients participating for more than 2 weeks, none had an apparent reduction of BPRS or CGI scores. Side effects were agitation, akathisia and emesis in single patients. After withdrawal of SCH 39166 of the patients improved when treated with classical neuroleptics or clozapine. The result of the study does not support the prediction that selective D1 dopamine receptor antagonism will produce antipsychotic effects in schizophrenia.