Antidotal effect of 4-aminopyridine on acute poisoning induced by magnesium sulfate

In anesthetized cats, the toxic effects, such as hypotension, respiratory failure and depression of anterior tibialis muscle twitches, induced by MgSO4 were promptly antagonized by iv 4-aminopyridine 0.6-1.3 mg/kg. In mice, 4-AP (3.0 mg/kg, ip) increased the LD50 of sc MgSO4 from 645 to 1062 mg/kg. Concurrent injections of 4-AP and CaCl2 in suitable dose levels showed a synergistic antidotal effect. 4-AP (1.5-2.0 mg/kg iv in divided doses) protected the conscious rabbits, which had been given lethal dose (650 mg/kg, im) of MgSO4, from death. Experiments on phrenic nerve discharge in anesthetized rabbits and rat phrenic nervediaphragm praparations revealed that the occurrence of respiratory failure during Mg2+ intoxication was due to neuromuscular blockade, not due to respiratory center depression, and the respiratory recovering effect of 4-AP chiefly resulted from its neuromuscular transmission facilitating effect.