Neuroendocrine effects of quetiapine in healthy volunteers.
The present study measured prolactin, cortisol, ACTH and growth hormone in healthy male volunteers following an acute oral administration of quetiapine, an atypical antipsychotic with high affinity for H1 and moderate affinity for sigma, alpha1, 5-HT2, alpha2 and D2 receptors. Fifteen male volunteers entered this randomized double-blind, cross-over, placebo-controlled study. Blood samples were drawn every 30 min from 09:00 hours to 13:00 hours. The first samples were drawn immediately before the administration of 150 mg quetiapine or placebo. Mean results for each hormone and ANOVA for repeated measures were performed. The area under the curve (AUC) hormonal values were calculated and compared by paired t test. The ANOVA showed an increase of prolactin after quetiapine administration from time 60 min up to the end of the observation period. Cortisol decreased after quetiapine administration from time 150 min to time 240 min. ACTH secretion showed no difference compared to placebo. There was a late increase in growth hormone secretion, significant in comparison with placebo only at time 210 min. The AUC values were statistically different for prolactin and cortisol compared to placebo. A single dose of quetiapine (150 mg) increased prolactin secretion probably due to a transiently high D2 receptor occupancy at the anterior pituitary. Cortisol secretion decreased as was expected from quetiapine's pharmacodynamic profile. The lack of response of ACTH might be, at least in part, explained by the low hormonal assay sensitivity. The late growth hormone increase might have been due to quetiapine's antagonism of H1 receptors.
Department of Psychobiology, Federal University of São Paulo, São Paulo School of Medicine, São Paulo, Brazil.
Alexandro
A
de Borja Gonçalves Guerra
Saulo
S
Castel
Ana Amélia
AA
Benedito-Silva
Helena Maria
HM
Calil
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D011388:Prolactin / Q000097:blood*; D000069348:Quetiapine Fumarate; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000502:physiology
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D017448:Receptors, Dopamine D2; D011969:Receptors, Histamine H1; D044348:Receptors, Serotonin, 5-HT2; D019382:Human Growth Hormone; D000069348:Quetiapine Fumarate; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone