de Borja Gonçalves Guerra Alexandro, Castel Saulo, Benedito-Silva Ana Amélia, Calil Helena Maria
Department of Psychobiology, Federal University of São Paulo, São Paulo School of Medicine, São Paulo, Brazil.
Int J Neuropsychopharmacol. 2005 Mar;8(1):49-57. doi: 10.1017/S1461145704004705. Epub 2004 Oct 7.
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.
本研究对健康男性志愿者口服一剂非典型抗精神病药物喹硫平（对H1受体具有高亲和力，对σ、α1、5-HT2、α2和D2受体具有中等亲和力）后体内的催乳素、皮质醇、促肾上腺皮质激素（ACTH）和生长激素进行了测定。15名男性志愿者参与了这项随机双盲、交叉、安慰剂对照研究。从09:00至13:00每30分钟采集一次血样。第一批样本在服用150mg喹硫平或安慰剂之前即刻采集。对每种激素的平均结果进行了分析，并对重复测量数据进行了方差分析（ANOVA）。通过配对t检验计算并比较了激素的曲线下面积（AUC）值。方差分析显示，服用喹硫平后，从60分钟开始直至观察期结束，催乳素水平升高。服用喹硫平后，从150分钟至240分钟，皮质醇水平下降。与安慰剂相比，ACTH分泌无差异。生长激素分泌出现延迟增加，仅在210分钟时与安慰剂相比有显著差异。与安慰剂相比，催乳素和皮质醇的AUC值在统计学上有差异。单剂量喹硫平（150mg）可能由于垂体前叶D2受体短暂高占有率而增加了催乳素分泌。正如喹硫平的药效学特征所预期的那样，皮质醇分泌减少。ACTH缺乏反应可能至少部分是由于激素检测灵敏度较低所致。生长激素的延迟增加可能是由于喹硫平对H1受体的拮抗作用。
