Mouse Foot Screen for the Inhibition of Sweating by Anticholinergic Drugs

Abstract

Mice have been utilized to develop a simple, rapid, inexpensive, quantitative screening procedure for sweat inhibition by anticholinergic agents. Graded doses of anticholinergic drugs are injected with a microliter syringe subcutaneously under the plantar foot pads of one hind foot of mice. Both hind feet are then coated with a suspension of starch and castor oil, and the mice are stimulated to sweat by an intraperitoneal injection of 10 mg/kg of pilocarpine HCI. Sweating on the treated foot is judged to be inhibited or not inhibited relative to the contralateral untreated foot. The median inhibitory concentrations and 95% confidence limits are determined by a simple, approximate method. The relative potencies of test compounds are expressed in terms of their ratios to a standard, scopolamine HBr. Compounds representing a wide range of potencies have been screened, and significant differences in their sweat inhibiting potencies have been demonstrated. These compounds include, in order of decreasing activity: tridihexethyl chloride and (2-[2-methyl-1-pyrrol- idyl ]ethylphenylcyclopentylacetate) HCI, which have similar potencies, 3, 3-diphenyl-N- dimethylpropylamine HCI and hydroxyzine HCI.