A comparison of the effects of 4-dimethylaminopyridine and 4-aminopyridine on isolated cardiac and skeletal muscle preparations.

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.