Yamamoto M, Shimizu M, Okamiya H
Department of Pharmacology, Central Research Laboratories, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
Eur J Pharmacol. 1990 Jun 8;181(3):207-14. doi: 10.1016/0014-2999(90)90080-p.
The cerebral protective actions of a new thyrotropin releasing hormone (TRH) analogue, YM-14673, [Na-[[(S)-4-oxo-2-azetidinyl-carbonyl]-L-histidyl-L-prolinamide] dihydrate), were compared with those of CDP-choline (cerebral metabolic enhancer) and naloxone in rats rats subjected to unilateral carotid artery ligation and anoxic exposure (Levine rats). Drugs were administered intraperitoneally or orally 20, 80, and 140 min after anoxia. YM-14673 (0.03 to 1 mg/kg i.p. and 0.3 to 10 mg/kg p.o.) decreased the incidence of neurological deficits, such as hemiplegia and convulsion followed by coma and death, for 48 h after ischemia and anoxia. Both the increase in the brain water content and the degeneration of neurons in the cerebral cortex and thalamus were prevented by YM-14673 at a dose of 0.1 mg/kg (i.p.). CDP-choline (400 mg/kg i.p.), which is currently used in the therapy of cerebral vascular diseases, and naloxone (3 mg/kg i.p.) also decreased the incidence of the neurological deficits. These results suggest that YM-14673 protects Levine rats against neurological deficits, presumably by attenuating the development of brain edema and preventing neuronal damage. This compound may be useful in the therapeutic treatment of cerebral vascular diseases.
一种新型促甲状腺激素释放激素（TRH）类似物YM - 14673（二水合钠[[(S)-4-氧代-2-氮杂环丁烷基-羰基]-L-组氨酰-L-脯氨酰胺]）的脑保护作用，在单侧颈动脉结扎和缺氧暴露的大鼠（Levine大鼠）中与胞磷胆碱（脑代谢增强剂）和纳洛酮进行了比较。在缺氧后20、80和140分钟腹腔内或口服给药。YM - 14673（腹腔注射0.03至1毫克/千克，口服0.3至10毫克/千克）降低了缺血和缺氧后48小时神经功能缺损的发生率，如偏瘫、惊厥，随后是昏迷和死亡。YM - 14673以0.1毫克/千克（腹腔注射）的剂量可防止脑含水量增加以及大脑皮层和丘脑神经元的变性。目前用于治疗脑血管疾病的胞磷胆碱（腹腔注射400毫克/千克）和纳洛酮（腹腔注射3毫克/千克）也降低了神经功能缺损的发生率。这些结果表明，YM - 14673可保护Levine大鼠免受神经功能缺损，可能是通过减轻脑水肿的发展和防止神经元损伤。这种化合物可能对脑血管疾病的治疗有用。
