Mechanism of the antagonism by 5-hydroxytryptamine of the toxicity due to certain cholinergic blocking agents

Abstract

Hydroxytryptamine has been reported as an antagonist of in vivo neuromuscular paralysis in mice. Experiments to elucidate the mechanism of interaction between 5-hydroxytryptamine and cholinergic blocking agents were conducted. Cholinergic blocking agents tested were botulinum toxin, d-tubocurarine, nereistoxin and hemicholinium. 5-hydroxytryptamine was most effective in antagonizing in vivo cholinergic blockade about 1 hr after its injection. It was also found that 5-hydroxytryptamine lowered body temperature most effectively 1 hr after its injection. Agents other than 5-hydroxytryptamine, namely sodium pentabarbitone and formaldehyde, also lowered body temperature and antagonized in vivo neuromuscular paralysis. It is proposed that the prolonged survival of mice treated with 5-hydroxytryptamine and then challenged was a result of depressed body temperature with a concomitant slowing in the binding and/or activity of cholinergic blocking agents. In addition to hypothermia, edema was detected in rats and mice treated with 5-hydroxytryptamine. Further experiments are suggested to determine whether edema facilitates or antagonizes the hypothermic effect.