title: A comparison of the effects of 4-dimethylaminopyridine and 4-aminopyridine on isolated cardiac and skeletal muscle preparations.
abstract: The actions of 4-dimethylaminopyridine (4-dimethyl-AP) on the isolated rat diaphragm and guinea-pig atria were examined and compared with those of 4-aminopyridine (4-AP). In the rat diaphragm, 4-dimethyl-AP slightly (27%) increased indirectly evoked maximal twitches, and was a weak antagonist of d-tubocurarine-induced neuromuscular block, while 4-AP increased indirect twitches by about 250%, and produced rapid and complete reversal of d-tubocurarine block. In directly stimulated preparations, 4-AP but not 4-dimethyl-AP produced marked augmentation of maximal twitches (220%). In electrically-driven guinea-pig left atria, both compounds produced positive inotropic effects (PIE), which were partially inhibited by L-propranolol or by pretreatment with intraperitoneal syrosyngopine or 6-hydroxydopamine, suggesting that part of the response was due to noradrenaline (NA) release. Nifedipine or methoxyverapamil (D-600) produced negative inotropic effects (NIE) and prevented the PIE of both aminopyridines. The NIE of these Ca2+ entry blockers was reversed by excess CaCl2 or NA. It is concluded that 4-dimethyl-AP, like 4-AP is a powerful cardiac inotropic agent in vitro. 4-Dimethyl-AP which, unlike 4-AP, possesses weak effects on neuromuscular transmission and on muscle contractility in the rat diaphragm, therefore appears to possess a greater specificity for cardiac muscle.
authors.forename: A O
authors.initials: AO
authors.lastname: Savage
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D003964:Diaphragm / Q000187:drug effects; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014403:Tubocurarine / Q000037:antagonists & inhibitors
chemical_list: D000631:Aminopyridines; D006892:Hydroxydopamines; D005711:Gallopamil; D012110:Reserpine; D016627:Oxidopamine; D015761:4-Aminopyridine; D009543:Nifedipine; C003885:4-dimethylaminopyridine; D014403:Tubocurarine; D009638:Norepinephrine