Differences in Actions of 4-Aminopyridine and 4-Methyl-2-Aminopyridine

Add time:09/05/2019    Source:sciencedirect.com

Publisher SummaryThis chapter discusses a study to analyze differences in actions of 4-aminopyridine (4AP) and 4-methyl-2-aminopyridine (4M2AP). Studies mainly with 4M2AP led von Haxthausen (1955) to conclude that aminopyridines had sympathomimetic effects. While 4M2AP shares convulsant and other actions with aminopyridines, it differs in some important respects. In rat diaphragm and chick biventer cervicis preparations, 4M2AP increased responses to nerve stimulation and acetylcholine (ACh) but depressed responses to direct stimulation. In presence of neostigmine, the effect of 4M2AP on responses to nerve stimulation and ACh was greatly reduced. This suggests that 4M2AP facilitates neuromuscular transmission by inhibition of Cholinesterase rather than augmentation of ACh release. In isolated rabbit atria, 4AP had a positive inotropic effect unaffected by propranolol and a negative chronotropic effect abolished by atropine. In isolated cat atria, 4AP decreased both force and rate and these effects were reversed by atropine. In contrast, 4M2AP increased rate and force in both species and these effects were greatly reduced by propranolol. It is concluded that both compounds have a direct positive inotropic effect but in addition 4AP increases spontaneous release of Ach, while 4M2AP releases noradrenaline.

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