Barbiturate-Coriamyrtin Antagonism

Abstract

At the time when we established the antidotal action of picrotoxin on the barbiturates 1 we indicated our intention of investigating the action of other picrotoxin-like substances. This paper reports the antidotal action of coriamyrtin in rabbits subjected to lethal doses of amytal, pernoston and nembutal.

The same method of procedure was followed in this work as in our early investigations of picrotoxin. 1 , 2 The animals were given single lethal doses of the barbiturate in increasing increments up to the limit of effective therapeusis and as soon as narcosis occurred coriamyrtin was administered in fractional doses at intervals P.R.N.

The initial dose of coriamyrtin was so graded as to elicit a mild state of reflex stimulation, evidenced by an increased rate of respiration and a manifestation of such gross reflexes as the whisker twitch, winking and (or) nystagmus, jerking movements of the limbs and ears, and coarse body tremors. Great care was taken in the lower barbituratized groups to grade the initial dose of coriamyrtin so as to avoid throwing the animal into violent convulsions. Mild seizures in such cases are inconsequential and pass off within a few minutes. When the respiration rate became slow again and the gross reflexes disappeared, to determine the degree of depression pinching the tip of the tail or ear was done. This served as an index for the quantitative estimation of the succeeding dose of coriamyrtin. Our technique was to try to maintain such a degree of sensitivity as to elicit a reaction of resistance to this mechanical mode of stimulation at all times. This procedure was repeated until the effects of the barbiturate were palpably beginning to wear off, as evidenced by the persistence of the induced hypersensitivity. The barbiturates were administered intraperitoneally as a 5% aqueous solution while the coriamyrtin was injected intravenously as a 0.1% solution.