Nemeroff C B, Prange A J, Bissette G, Breese G R, Lipton M A
Psychopharmacol Commun. 1975;1(3):305-17.
Previous work has demonstrated that thyrotropin-releasing hormone (TRH) and its beta-alanine analogue (beta-ala TRH) are potent antagonists of barbiturate-induced sedation. This study sought to determine the effects of these oligopeptides on the anticonvulsant properties of phenobarbital in the maximal electroshock seizure (MES) test. Pro-leu-gly-NH2, another hypothalmic peptide was also examined. None of the peptides studied had any anticonvulsant properties of their own, but TRH and beta-ala TRH, though not pro-leu-gly-NH2, potentiated the anticonvulsant potency of phenobarbital. Thyrotropin (TSH) and tri-iodothyronine (T3) were in effective, suggesting that the effects observed with TRH are not mediated via the pituitary-thyroid axis. Since phenobarbital treatment of grand mal epilepsy is often limited by sedation and since TRH antogonizes sedation and enhances anticonvulsant effects of the barbiturate, the hormone or a congener may find value as an adjunct in therapy.
先前的研究表明，促甲状腺激素释放激素（TRH）及其β-丙氨酸类似物（β-ala TRH）是巴比妥类药物所致镇静作用的有效拮抗剂。本研究旨在确定这些寡肽在最大电休克惊厥（MES）试验中对苯巴比妥抗惊厥特性的影响。同时也对另一种下丘脑肽脯氨酸-亮氨酸-甘氨酸-酰胺（Pro-leu-gly-NH2）进行了研究。所研究的这些肽自身均无抗惊厥特性，但TRH和β-ala TRH可增强苯巴比妥的抗惊厥效力，而Pro-leu-gly-NH2则无此作用。促甲状腺激素（TSH）和三碘甲状腺原氨酸（T3）无效，这表明TRH所观察到的作用并非通过垂体-甲状腺轴介导。由于苯巴比妥治疗大发作型癫痫常因镇静作用而受到限制，且TRH可拮抗镇静作用并增强巴比妥类药物的抗惊厥效果，因此该激素或其类似物可能作为辅助治疗药物具有应用价值。
