Interaction between the inhibitory effects of morphine and clonidine on intestinal transit in mice
Wong, C.L.
Methods and Findings in Experimental and Clinical Pharmacology 13(4): 249-254
1991
ISSN/ISBN: 0379-0355 PMID: 1875773 Document Number: 379680
Both clonidine and morphine dose-dependently inhibited intestinal transit in mice. This inhibitory effect of clonidine was antagonized by prior administration of yohimbine but not by naloxone, while morphine's effect was antagonized by both yohimbine and naloxone. Morphine pretreatment did not induce any apparent tolerance to the effect of clonidine and morphine tested 4 h later. However, yohimbine became more potent in antagonizing the effect of clonidine while naloxone remained ineffective. Morphine pretreatment enhanced the antagonistic effectiveness of both yohimbine and naloxone against morphine. Clonidine pretreatment at a dose that did not induce any tolerance slightly enhanced the antagonistic effects of yohimine and naloxone against morphine. Yohimbine also became more effective against clonidine but naloxone remained ineffective. At higher doses of clonidine pretreatment tolerance to the effects of morphine and clonidine were observed. These results suggest that both .alpha.2-adrenoceptors and opioid receptors are involved in the inhibitory action of morphine on intestinal transit, while clonidine mainly acts through the .alpha.2-adrenoceptors. In addition, there is a close interaction between the .alpha.2-adrenoceptors and opioid receptors in the intestine.