DUAL ACTION OF CLONIDINE ON ETHANOL-INDUCED GASTRIC-LESIONS - IS THE IMIDAZOLINE-PREFERRING RECEPTOR INVOLVED

The imidazole alpha-2-adrenoceptor agonist, clonidine, exerts a dual action on ethanol-induced gastric lesions. At lower doses, it has a gastroprotective effect which is also seen with two other alpha-2-adrenoceptor agonists - the catecholamine, alpha-methyldopa and the guanidine, guanabenz. The gastroprotective action of the three drugs is prevented by the selective alpha-2-adrenoceptor antagonist, yohimbine, suggesting that the action is mediated by alpha-2-adrenoceptors. However, at higher doses clonidine aggravates ethanol-induced gastric lesions, an effect also seen with another imidazole, oxymetazoline. The aggravating action is not prevented by yohimbine and is not seen with alpha-methyldopa and guanabenz. This suggests that it involves a receptor/mechanism other than alpha-2 - possibly an imidazoline-preferring receptor but further work, including radioligand binding studies, is needed to confirm this.