COMPARISON OF THE PHARMACOLOGICAL ACTIONS OF SOME NEW 4-AMINOPYRIDINE DERIVATIVES

The pharmacological actions of 2,4-diaminopyridine (2,4-DAP) and 3-[(dimethylamino)-carbonyl] amino 4-aminopyridine (LF-14) were examined and compared with those of 4-aminopyridine (4-AP) in anesthetized rats and on isolated rat and guinea pig tissues. Both compounds were more potent than 4-AP in reversing the neuromuscular block caused by pancuronium bromide. The ED50 of LF-14, 2,4-DAP and 4-AP were 100 .mu.g/kg, 140 .mu.g/kg and 450 .mu.g/kg, respectively. LF-14 and 2,4-DAP were also more potent in their in vitro actions on the neuroeffector junctions in the ileum and the isolated heart. 2,4-DAP and LF-14 either did not facilitate or only slightly facilitated the recovery time from xylazine/ketamine anesthesia which was used as a test for their central action; 4-AP significantly reduced the recovery time both 2,4-DAP and LF-14 are stronger peripherally acting compounds with less central action, and they they may be possible replacements for 4-AP as antagonists of non-depolarizing muscle relaxants.