Adrenergic Inhibition and Lethal Effect of Bacterial Endotoxin in Mice

Abstract

The protective effects of various types of adrenergic inhibition have been tested against the lethal action of injected bacterial endotoxin in mice. Preliminary experiments substantiated the abilities of phenoxybenzamine hydrochloride to block the lethal effect of injected epinephrine and of cocaine to augment its toxicity. 3,4- Dichloroisoproterenol also increased the lethal effect of epinephrine. TM 10 or 2,6-xylyloxyethyltrimethylammonium bromide had no effect acutely but offered a low order of protection when given 24 hours before the epinephrine. Reserpine also protected when given 24 hours in advance. Iproniazid was without effect. The only compound to give significant protection against bacterial endotoxin was 3,4-dichloroisoproterenol. This substance has been shown by previous workers to block inhibitor and vasodilator effects of epinephrine. Such effects are probably metabolic in nature and may concern carbohydrate metabolism.