Arblaster C I, Cameron D W, Lavi Y, Laycock G M, Shulman A
Unit of Medical Chemistry, University of Melbourne, Australia.
Methods Find Exp Clin Pharmacol. 1988 Mar;10(3):177-211.
The present study explores pharmacologically on the model spontaneously beating 3H-noradrenaline pretreated guinea-pig atrial preparation the mechanism(s) by which the representative central nervous system (CNS) stimulant drug 3-methyl-3-ethylglutarimide (bemegride, MEG) and its representative CNS depressant homologue 3-methyl-3-n-butylglutarimide (MBG) affect transmitter release and the force and rate of atrial contraction and contracture, as well as the relevance of these atrial mechanism(s) to those involved in the production of drug-evoked convulsions and hypnosis in the mammalian CNS. The process(es) involved in the interaction of MEG and MBG on the atrial preparation have also been studied to provide insight into possible CNS mechanism(s) that may be involved in the related central phenomena of drug-induced analepsis and anticonvulsant action. It would appear that the actions and interactions of MEG and MBG on the atrium and in the mouse both depend critically on glutarimide-evoked enhancement (MEG) or inhibition (MBG) of Ca2+ flux through potential-operated Ca2+ channels located primarily on the responsive atrial sarcolemmal and neuronal synaptic membranes, respectively. In addition, it seems likely that the reciprocal antagonism shown by these substances on the atrium and in the CNS is predominantly functional in nature. The pharmacological and clinical implications of these findings are discussed, with particular reference to the possible benefit of selective calcium antagonists and related drugs in the management of drug dependence and withdrawal.
本研究在3H-去甲肾上腺素预处理的豚鼠自发性搏动心房标本模型上，从药理学角度探讨了具有代表性的中枢神经系统（CNS）兴奋药3-甲基-3-乙基戊二酰亚胺（美解眠，MEG）及其代表性的CNS抑制同系物3-甲基-3-正丁基戊二酰亚胺（MBG）影响递质释放、心房收缩和挛缩的力量及速率的机制，以及这些心房机制与哺乳动物CNS中药物诱发惊厥和催眠产生机制的相关性。还研究了MEG和MBG在心房标本上的相互作用过程，以深入了解可能参与药物诱发的苏醒和抗惊厥作用等相关中枢现象的中枢神经系统机制。看来，MEG和MBG在心房及小鼠体内的作用和相互作用都主要取决于戊二酰亚胺分别诱发的通过主要位于反应性心房肌膜和神经元突触膜上的电压门控Ca2+通道的Ca2+内流增强（MEG）或抑制（MBG）。此外，这些物质在心房和中枢神经系统中表现出的相互拮抗作用似乎主要是功能性的。本文讨论了这些发现的药理学和临床意义，特别提及了选择性钙拮抗剂及相关药物在药物依赖和戒断管理中可能带来的益处。
