The effect of olanzapine treatment on m-chlorophenylpiperazine-induced hormone release in schizophrenia.
In addition to dopamine, serotonin (5-hydroxytryptamine, 5-HT) has been reported to play an important role in schizophrenia. Besides blocking dopamine, atypical antipsychotics also block 5-HT receptors. The clinical efficacy of the atypical antipsychotic clozapine is associated with the 5-HT antagonistic action of the drug and a high serotonergic tone before treatment. The atypical antipsychotic olanzapine has a receptor-binding profile similar to that of clozapine. The present study investigated whether treatment with olanzapine blocks hormone release induced by the 5-HT2c agonist m-chlorophenylpiperazine (m-CPP) and, if so, whether this 5-HT antagonistic effect is related to treatment response. Eighteen male schizophrenic patients participated in this study. All patients were challenged with m-CPP (0.5 mg/kg orally) in a double-blind, randomized, placebo-controlled design after a drug-free period of at least 2 weeks. Adrenocorticotropic hormone (ACTH), cortisol, and prolactin plasma levels were measured every 30 minutes up to 210 minutes after challenge. Patients were treated for 6 weeks with 10 mg olanzapine daily in an open design, after which the challenge tests were repeated. Olanzapine significantly blocked m-CPP-induced ACTH, cortisol, and prolactin release, suggesting that it is a potent 5-HT2c antagonist in vivo. This 5-HT antagonistic effect of olanzapine was not significantly correlated with treatment response. Also, no significant correlation was found between m-CPP-induced hormone release before treatment and clinical response after treatment with olanzapine. These findings suggest that olanzapine is a potent 5-HT2c antagonist in vivo but that this is unrelated to its clinical efficacy in this nonrefractory sample of schizophrenic patients.
Scheepers
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University Medical Center, Department of Psychiatry, Utrecht, The Netherlands. f.scheepers@psych.azu.nl
Gespen de Wied
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Kahn
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D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001569:Benzodiazepines; D004311:Double-Blind Method; D006728:Hormones / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D008297:Male; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000502:physiology; D012559:Schizophrenia / Q000097:blood*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D000324:Adrenocorticotropic Hormone; D001569:Benzodiazepines; D006728:Hormones; D006854:Hydrocortisone; D000077152:Olanzapine; D010879:Piperazines; D010890:Pirenzepine; D011388:Prolactin; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C015068:1-(3-chlorophenyl)piperazine