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 anaesthetized 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 ED50S of LF-14, 2,4-DAP and 4-AP were 100 micrograms/kg, 140 micrograms/kg and 450 micrograms/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 anaesthesia which was used as a test for their central action; 4-AP significantly reduced the recovery time. We therefore conclude that both 2,4-DAP and LF-14 are stronger peripherally acting compounds with less central action, and that they may be possible replacements for 4-AP as antagonists of non-depolarizing muscle relaxants.
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects; D012995:Solubility; D013997:Time Factors
D000631:Aminopyridines