THE SYNERGISM OF ANESTHETICS AND HYPNOTICS WITH CURARE AND CURARE-LIKE ALKALOIDS

¹ From the Merck Institute for Therapeutic Research, Rahway, New Jersey

1. Premedication of mice and cats with small doses of ether, phenobarbital sodium, or pentobarbital sodium enhances the sensitivity of the animal to d-tubocurarine chloride, strychnos curare (Merck), dihydro--erythroidine hydrobromide and quinine methochloride or quinine ethochloride but not to quinine salts. Sub-effective amounts of these curare-like alkaloids have a paralyzing effect on mice and cats so premedicated. The effective doses of curare and the curare-like alkaloids for the pretreated animals are 1/10 to of the dose necessary to produce a similar paralyzing effect in untreated animals. There is a reciprocal relationship between the amounts of the alkaloids and hypnotics necessary to produce this synergistic effect.

2. Premedication with urethane, papaverine hydrochloride or scopolamine chloride produces no distinct sensitivity for the aforenamed curare-like alkaloids. Pretreatment with morphine increases the effect of these curare substances in mice, but produces only a doubtful effect in cats and rabbits.

3. Subcutaneous administration of curare and the curare-like alkaloids produced sensitization in mice, but not in cats. In this latter species intravenous injection of curare is highly effective.

4. Premedication with anesthetics (ether) or hypnotics (barbiturates) followed by injection of curare alkaloids seems to be justified from a practical point of view since it produces an increased sensitivity to the curare drugs and thus permits attainment of a degree of muscular relaxation which cannot be obtained with the same amount of curare alone.