ADH-Like Effect of Tranquilizers in Amphibians. ∗

Abstract

Summary

Seventeen tranquilizers were studied for their ADH-releasing effect of inducing increased water uptake and body weight gain in Bufo viridis and Rana pipiens. In intact amphibians phenothiazine derivatives produced a varying degree of increased water uptake through the skin. Chlorpromazine was found to be even more effective than either exogenous ADH (pitressin) or pituitary homogenates since its effect lasted for 24–48 hours. Phenothiazine derivatives with a Cl-atom at position 2 and a dimethylamino-propyl side-chain at position 10 gave the maximum effect. On the other hand, substitution of Cl at position 2 by H, CF₃ or OCH₃, or of the dimethylamino-propyl group by a branched chain, or a piperazinepropyl group, reduced the ADH-like effect. Other tranquilizers, such as chlordiazepoxide (Librium), meprobamate, benactyzine, reserpine showed no significant effect. Treatment of hypophysectomized toads and frogs with chlorpromazine produced a very weak effect, apparently due to ADH release from the hypothalamus only. On the basis of the above findings it is suggested that through the action of tranquilizers on the hypothalamus, ADH hypersecretion from the hypothalamus and release from the posterior pituitary can be effected, resulting in an increased water uptake and body weight gain in Bufo toads and Rana frogs.