D-fenfluramine-evoked serotonergic responses in olanzapine-treated schizophrenic patients.
Antagonist activity at the 5-HT(2) receptor may contribute to the therapeutic efficacy of atypical antipsychotics in schizophrenia. This neuroendocrine study examined the in vivo functional serotonergic (5-HT) activity of the atypical antipsychotic olanzapine. We examined central 5-HT(2) responses by measuring the serum prolactin (PRL) over 5 h in response to 30 mg of D-fenfluramine (DFEN) in two groups of male schizophrenic patients. Blunted PRL responses to DFEN indicate functional 5-HT(2) receptor antagonism. Seven patients treated with olanzapine at a mean (S.D.) dose of 13.1 (4.6) for a mean of 28 weeks were compared with a matched group of eight patients who had received no antipsychotic treatment for at least 2 weeks. Baseline PRL levels did not differ significantly in the two patient groups and were within the normal range. The olanzapine-treated patients showed a significantly lower maximal DFEN-evoked PRL response and a significantly lower group x time overall PRL release compared with the untreated patient group. We have previously demonstrated a similar degree of functional in vivo 5-HT(2) antagonism with the atypical antipsychotic clozapine. This study thus suggests that this activity may not contribute to the unique clinical efficacy of clozapine.
Jones
Hugh
H
Institute of Psychiatry, De Crespigny Park, London, SE5 8AF UK.
Curtis
Vivienne A
VA
Wright
Padraig
P
Pilowsky
Lyn S
LS
Lucey
James V
JV
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D005277:Fenfluramine; D000077152:Olanzapine; D010890:Pirenzepine; D011388:Prolactin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors