Matsushita M, Yonemori F, Furukawa N, Ohta A, Toide K, Uchida I, Iwata K
Department of Pharmacology, Japan Tobacco Inc., Kanagawa.
Arzneimittelforschung. 1993 Aug;43(8):813-7.
The central nervous system (CNS) effects of a novel thyrotropin-releasing hormone (TRH) analogue, JTP-2942 (Na-alpha- ((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-pro linamide monohydrate, CAS 131404-34-7) were investigated and compared with those of TRH. When administrated subcutaneously, JTP-2942 was about 80 times more potent than TRH in the antagonization of reserpine-induced hypothermia, and when administrated intravenously it was about 16 times more potent than TRH in the potentiation of flexor reflexes. Furthermore, oral administration of JTP-2942 was able to antagonize a chlorpromazine-induced reduction in locomotor activity, while TRH was far less effective. In tests on the recovery from pentobarbital-induced sleep and disturbance of consciousness induced by concussive head trauma, JTP-2942 was about 30 and 3 times more potent than TRH, respectively. Thus, JTP-2942 had a far stronger and more persistent action compared with TRH in regard to these effects. However, JTP-2942 had a 3-fold lower effect on thyroid stimulating hormone (TSH) release than TRH. These results suggest that the stimulatory effects of JTP-2942 are selective for the CNS and that this TRH analogue may be applicable to clinical use.
研究了一种新型促甲状腺激素释放激素（TRH）类似物JTP-2942（Na-α-((1S,2R)-2-甲基-4-氧代环戊基羰基)-L-组氨酰-L-脯氨酰胺一水合物，CAS 131404-34-7）对中枢神经系统（CNS）的作用，并与TRH进行了比较。皮下给药时，JTP-2942在拮抗利血平诱导的体温过低方面比TRH强约80倍，静脉给药时，在增强屈肌反射方面比TRH强约16倍。此外，口服JTP-2942能够拮抗氯丙嗪诱导的运动活性降低，而TRH的效果则差得多。在戊巴比妥诱导的睡眠恢复和脑震荡性头部创伤引起的意识障碍测试中，JTP-2942分别比TRH强约30倍和3倍。因此，就这些作用而言，JTP-2942与TRH相比具有更强、更持久的作用。然而，JTP-2942对促甲状腺激素（TSH）释放的作用比TRH低3倍。这些结果表明，JTP-2942的刺激作用对中枢神经系统具有选择性，并且这种TRH类似物可能适用于临床。
