Abstract

On simultaneous intraperitoneal injection in the mouse, the quaternary oximes, Protopam (2-PAM) and TMB4 raised the lethal dose of Phospholine by factors of 24 and 220 respectively. Protopam rapidly reversed the muscarinic and nicotinic effects of Phospholine in the anesthetized cat on heart rate, blood pressure, respiration and isometric twitch tension of indirectly stimulated skeletal muscle. In survival experiments in cats, Protopam was preferred over atropine and Probanthine as an antidote against Phospholine toxicity since it immediately restored spontaneous respiration, but the latter drugs were also effective when given together with artificial respiration.

Protopam reacts with Phospholine in vitro but probably too slowly to account for its antidotat action. Both Protopam and TMB4 reactivate Phospholine-inhibited acetylcholinesterase of whole mouse blood rapidly in the continued presence of inhibitor and resistance of the enzyme to Phospholine is maintained after dilution of the oxime to an ineffective level. It appears that enzyme reactivation must be considered a significant factor in the antidotal action in vivo.

Neostigmine, Mestinon and Humorsol were slightly protected by simultaneous administration of Protopam or TMB4. In each case the latter was more effective than the former. The lethal doses of Mytelase and Tensilon were not significantly modified by the oximes.

Phospholine and Mytelase exhibited mutual potentiation of toxicity by a factor of 53 or 186 depending upon the experimental conditions. Minor potentiation was also seen among some of the other drugs studied.