Kuenzel Heike E, Steiger Axel, Held Katja, Antonijevic Irina A, Frieboes Ralf-Michael, Murck Harald
Department of Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804, Munich, Germany.
Psychopharmacology (Berl). 2005 Jul;180(2):327-32. doi: 10.1007/s00213-005-2160-3. Epub 2005 Feb 17.
Sarizotan is a 5-HT(1A) agonist with high affinity to D(3) and D(4) receptors. In animal experiments, the drug shows a strong anti-cataleptic effect and suppresses effectively dyskinesias in animal models of L: -dopa-induced dyskinesia and of tardive dyskinesia. Data from an open pilot study in patients with Parkinson's disease show clear indication of a treatment effect against L: -dopa-induced dyskinesia.
CNS-active drugs are known to modulate sleep electroencephalogram (EEG) and sleep-related hormone secretion. 5-HT(1A) agonists suppress rapid-eye movement (REM) sleep and enhance the secretion of ACTH, cortisol, prolactin and growth hormone (GH) at daytime. We hypothesised that sarizotan shares these effects. Furthermore, we were interested in the influence of sarizotan on leptin, which participates in the regulation of the energy balance and is enhanced after various psychoactive drugs.
Ten healthy male subjects were investigated twice in a double-blind, placebo-controlled crossover design. Sleep EEG and nocturnal hormone secretion of ACTH, cortisol, prolactin, GH and leptin were examined after oral administration of either placebo or 20 mg of sarizotan at night.
After administration of sarizotan, a significant reduction of REM sleep and total sleep time in conventional sleep EEG and a significant reduction of sigma- and theta-power in spectral analysis were observed. The main effect on nocturnal hormone secretion was a significant elevation of prolactin and of ACTH in the first half of the night.
While REM sleep was suppressed, the endocrine effects of 20 mg sarizotan at night were weak. Its sleep-endocrine profile is comparable to the effects provoked by selective 5-HT reuptake inhibitors.
沙立佐坦是一种对D(3)和D(4)受体具有高亲和力的5-羟色胺(1A)激动剂。在动物实验中，该药物显示出强大的抗僵住症作用，并能有效抑制左旋多巴诱发的运动障碍和迟发性运动障碍动物模型中的运动障碍。帕金森病患者的一项开放性初步研究数据明确显示了其对左旋多巴诱发的运动障碍的治疗效果。
已知中枢神经系统活性药物可调节睡眠脑电图(EEG)和与睡眠相关的激素分泌。5-羟色胺(1A)激动剂可抑制快速眼动(REM)睡眠，并在白天增强促肾上腺皮质激素(ACTH)、皮质醇、催乳素和生长激素(GH)的分泌。我们假设沙立佐坦也有这些作用。此外，我们还关注沙立佐坦对瘦素的影响，瘦素参与能量平衡调节，在使用各种精神活性药物后会增加。
10名健康男性受试者采用双盲、安慰剂对照交叉设计进行了两次研究。在夜间口服安慰剂或20mg沙立佐坦后，检测睡眠EEG以及ACTH、皮质醇、催乳素、GH和瘦素的夜间激素分泌情况。
服用沙立佐坦后，传统睡眠EEG中的REM睡眠和总睡眠时间显著减少，频谱分析中的σ波和θ波功率显著降低。对夜间激素分泌的主要影响是前半夜催乳素和ACTH显著升高。
虽然REM睡眠受到抑制，但夜间20mg沙立佐坦的内分泌作用较弱。其睡眠-内分泌特征与选择性5-羟色胺再摄取抑制剂引起的作用相当。
