ANTAGONISM OF THE ANTIAVOIDANCE EFFECTS OF VARIOUS AGENTS BY ANTICHOLINERGIC DRUGS

¹ Merck institute for Therapeutic Research, West Point, Pennsylvania

The antiavoidance activity of chiorpromazine, trifluoperazine, perphenazine, thioridazine, haloperidol, ethomoxane, chlorprothixene, tetrabenazine and reserpine in squirrel monkeys was found to be significantly reduced when administered with a concurrent dose of benztropine. In contrast, the antiavoidance activity of chiordiazepoxide, pentobarbital, meprobamate, chloral hydrate and paraldehyde was either unaffected or increased by concurrent benztropine administration. Benztropine, scopolamine, cyproheptadine, atropine and trihexyphenidyl reversed the antiavoidance activity of a standard dose of perphenazine; however, the peripheral anticholinergic actions of these compounds as measured by pupil dilatation were not found to be highly correlated with their action upon avoidance activity. This dichotomy was felt to be due to a difference in central vs. peripheral anticholinergic potency. In Macace speciosa the antiavoidance action of perphenazine could be reversed by the i. v. injection of benztropine. This reversal was considered strong evidence that the main effect seen was not due to inhibition of absorption, but attributable to a pharmacologic interaction of the compounds studied. Reversal of the antiavoidance activity of major tranquilizing compounds by anticholinergics may be a general attribute of this class of agents; it is suggested that this interaction may be useful in distinguishing these compounds from other types of depressants.