Activities in Vitro of 8-Substituted Derivatives of Adenosine-3′,5′-Cyclic Monophosphate on Guinea Pig Trachea and Rat Portal Vein

Abstract

Summary

Twelve 8-substituted analogs of cyclic AMP were tested on excised guinea pig trachea and rat portal vein; cyclic AMP, dibutyryl cyclic AMP, and theophylline were similarly tested. The 8-benzylthio, 8-methylthio, 8-azido, and 8-thio derivatives of cyclic AMP were among the most potent relaxants of both tracheal and venous smooth muscle. Each of these four analogs was: (a) more potent than dibutyryl cyclic AMP, but less potent than theophylline, on excised trachea; and (b) roughly equipotent to or less potent than either dibutyryl cyclic AMP or theophylline on excised vein. Several other 8-substituted derivatives of cyclic AMP, as well as cyclic AMP itself, were inactive as relaxants at concentrations of 400 μg/ml.

In general, the decreasing order of relaxant activity among the groups of 8-substituted analogs of cyclic AMP was 8-thio>8-oxo>8-amino.