Ogawa N, Mizuno S, Mori A, Kuroda H
Peptides. 1984 Jan-Feb;5(1):53-6. doi: 10.1016/0196-9781(84)90050-0.
Dihydroergotoxine (DHET) is comprised of equal part of the mesylates of dihydroergocristine, dihydroergocornine and dihydroergocryptine. In the standard radioreceptor assays, DHET components displaced the CNS-receptor binding of [3H]-enkephalin (ENK) and [3H]thyrotropin releasing hormone (TRH). The inhibitory effect of DHET on ENK binding was competitive, and an allosteric effect seems to be involved in the DHET inhibition of TRH binding to its receptor. Intraperitoneal injections of DHET (1 mg/kg/day) to aged rats for 14 days resulted in a significant increase of ENK and TRH binding in the cerebral cortex. Scatchard plots of saturation experiments indicate that the increase of ENK binding is due to the increased affinity of the binding sites, and the increase of TRH binding reflects an increase in numbers of binding sites. The results suggest that the therapeutic efficacy of DHET is derived initially from its effects on the ENK and TRH receptors especially in the cerebral cortex, which in turn influence the function of monoaminergic neurons.
双氢麦角毒碱（DHET）由等量的双氢麦角汀、双氢麦角柯宁和双氢麦角隐亭甲磺酸盐组成。在标准放射受体分析中，DHET的成分取代了[3H] - 脑啡肽（ENK）和[3H]促甲状腺激素释放激素（TRH）与中枢神经系统受体的结合。DHET对ENK结合的抑制作用是竞争性的，并且变构效应似乎参与了DHET对TRH与其受体结合的抑制。对老年大鼠腹腔注射DHET（1mg/kg/天），持续14天，导致大脑皮质中ENK和TRH结合显著增加。饱和实验的Scatchard图表明，ENK结合的增加是由于结合位点亲和力的增加，而TRH结合的增加反映了结合位点数量的增加。结果表明，DHET的治疗效果最初源于其对ENK和TRH受体的作用，尤其是在大脑皮质中，这反过来又影响单胺能神经元的功能。
