Reversibility of kanamycin-induced neuromuscular and cardiovascular depressions by 4-aminopyridine, in comparison with neostigmine.
Antagonistic actions of 4-aminopyridine (4-AP) and neostigmine methylsulfate (NSG) on the neuromuscular and cardiovascular depressions by kanamycin (KM) were studied in urethane anesthetized rats, in comparison with D-tubocurarine (D-Tc). Measured parameters were indirectly elicited twitch of tibialis anterior muscle, mean arterial pressure and heart rate. All parameters were progressively depressed by continual infusions (0.2 ml/min) of KM (70 mg/ml) and D-Tc (10 microgram/ml). 4-AP 2.8 mg/kg s.c. significantly antagonized these depressive actions of both of D-Tc and KM, while NSG 0.1 mg/kg s.c. significantly antagonized only those of D-Tc and more strongly than 4-AP did in cardiovascular depression. 4-AP could antagonize the complete neuromuscular blockade and lethality of KM to the equilevel of conscious rats and those of D-Tc to 2.78 and 1.78 time doses of conscious rats in the complete neuromuscular blocking dose and lethal dose respectively. These results suggest that the antagonistic action of 4-AP results from its facilitation activity in the neurotransmitter release and its augmentative activity in the muscle contractility and also indicate a possibility that 4-AP can be used as a relief agent for the neuromuscular and/or cardiovascular depressions induced by some aminoglycoside antibiotics and nondepolarizing neuromuscular blocking drug in the clinical aspect.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D003864:Depression, Chemical; D007612:Kanamycin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D008297:Male; D009388:Neostigmine / Q000494:pharmacology*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014403:Tubocurarine / Q000009:adverse effects / Q000037:antagonists & inhibitors
D000631:Aminopyridines; D009467:Neuromuscular Depolarizing Agents; D009388:Neostigmine; D007612:Kanamycin; D015761:4-Aminopyridine; D014403:Tubocurarine