Dopamine receptor responsivity in schizophrenic patients in a drug-free state and after treatment with olanzapine.
1. Olanzapine is a novel atypical antipsychotic with affinity for a number of neurotransmitter receptors including dopamine D1, D2, D4, serotonin 5HT2A, 5HT2C, histamine H1, a1-adrenergic, and muscarinic receptors. 2. A neuroendocrinological method to check the degree of dopamine receptor blocking is by measuring the prolactin (PRL) responses to acute (i.m.) administration of haloperidol (HAL). The authors applied this test in a group of male patients with DSM-IV schizophrenia in the drug-free state. The patients were subsequently treated with olanzapine (OLZ) (mean daily dose: 22.5+/-5.8) and the test was repeated six weeks later. For the HAL-test, 5mg HAL were injected i.m. and blood samples were taken at times 0, 30, 60, 90 and 120 minutes. Fourteen patients enrolled in the study. Psychopathology was assessed by means of the Brief Psychiatric Rating Scale (BPRS). 3. Six weeks treatment with OLZ resulted in significant decreases in the total BPRS score and on the score of its subscales for positive, negative, and general psychopathology. Comparison of the PRL response patterns, after HAL administration by analysis of variance for repeated measures (ANOVAR) for drug treatment and time, revealed a highly significant time effect (F=28.98, p=0.000) and a significant treatment by time interaction (F=8.27, p=0.000008). Namely, in the drug-free state significant increases were found in the PRL levels after i.m. HAL administration which were significantly reduced during treatment with OLZ, indicating moderate receptor blockade.
Lykouras
L
L
Athens University Medical School Department of Psychiatry, Eginition Hospital, Greece.
Markianos
M
M
Hatzimanolis
J
J
Oulis
P
P
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011388:Prolactin / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D010890:Pirenzepine; D011388:Prolactin; D006220:Haloperidol; D000077152:Olanzapine