THE PHARMACOLOGY OF ATRACURIUM: A NEW COMPETITIVE NEUROMUSCULAR BLOCKING AGENT

Abstract

Atracurium besylate, 2,2''-(3,11-dioxo-4,10-dioxatridecylene)-bis-[6,7-dimethoxy-1-(3,4-dimethoxy-benzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolinium] dibenzenesulphonate, is one of a new series of competitive neuromuscular blocking agents. An i.v. dose of 0.25 mg/kg produced complete paralysis in anesthetized cats, dogs and rhesus monkeys; paralysis was of medium duration and was readily antagonized by neostigmine. Vagal blockade occurred only after doses 8-16 times greater than the full neuromuscular paralyzing dose and effects on sympathetic mechanisms were minimal. Hypotension and bradycardia were evident after supramaximal doses of 4 mg/kg i.v. and these effects, together with circulatory depression, were probably attributable to histamine release. In vitro studies have shown that the non-enzymic decomposition of atracurium by Hofmann Elimination was enhanced by increasing pH. In vivo neuromuscular paralysis was significantly reduced when the arterial pH was increased. The liver and kidney are not important in the metabolism and elimination of unchanged drug. These results are of sufficient interest to merit the evaluation of atracurium in anesthetized man.