Hashimoto T, Wada T, Fukuda N, Nagaoka A
Research and Development Division, Takeda Chemical Industries Ltd., Osaka, Japan.
J Pharm Pharmacol. 1993 Feb;45(2):94-7. doi: 10.1111/j.2042-7158.1993.tb03690.x.
The mode of action and the time course of the effects of continuous thyrotropin-releasing hormone (TRH) treatment using a two-week sustained release injectable formulation of TRH-containing copoly((+/-)-lactic/glycolic acid) microspheres (TRH-SR) on pentobarbitone-induced sleeping time were studied in rats. Subcutaneous treatment with TRH-SR at doses corresponding to 0.05 and 0.2 mg of TRH kg-1 day-1 caused a dose-related shortening of pentobarbitone-induced sleeping time with a minimum effective dose (MED) of 0.05 mg kg-1 day-1, without affecting the body weight gain. On the other hand, the MED of TRH when given as a bolus subcutaneous injection was 40 mg kg-1. The effect of TRH-SR treatment was blocked by intraperitoneal scopolamine (0.1 mg kg-1) and mecamylamine (2 mg kg-1) but not by scopolamine methyl bromide (0.1 mg kg-1). The results indicate that continuous TRH treatment using TRH-SR causes shortening of pentobarbitone-induced sleeping time at doses lower than those required using bolus injection and probably by a mechanism involving the central cholinergic system.
使用含促甲状腺激素释放激素（TRH）的聚（±-乳酸/乙醇酸）共聚物微球（TRH-SR）的两周缓释注射制剂连续治疗促甲状腺激素释放激素（TRH）对戊巴比妥诱导睡眠时间的作用方式和时间过程在大鼠中进行了研究。以相当于0.05和0.2mg TRH kg-1天-1的剂量皮下注射TRH-SR，导致戊巴比妥诱导睡眠时间呈剂量相关缩短，最小有效剂量（MED）为0.05mg kg-1天-1，且不影响体重增加。另一方面，皮下推注TRH时的MED为40mg kg-1。TRH-SR治疗的效果被腹腔注射东莨菪碱（0.1mg kg-1）和美加明（2mg kg-1）阻断，但未被溴甲东莨菪碱（0.1mg kg-1）阻断。结果表明，使用TRH-SR连续治疗TRH可在低于推注注射所需剂量的情况下缩短戊巴比妥诱导的睡眠时间，其机制可能涉及中枢胆碱能系统。
