A study on the antagonism of the intestinal inhibitory effects of morphine and clonidine by yohimbine in mice.

In mice, clonidine administered subcutaneously caused a dose-dependent inhibition of the intestinal motility as assayed by the movement of a charcoal meal. This inhibitory effect of clonidine was antagonized dose-dependently by prior subcutaneous or intracisternal administration of yohimbine. However, yohimbine given intracerebroventricularly was ineffective in antagonising the intestinal inhibitory action of clonidine. Clonidine administered centrally, either intracisternally or intracerebroventricularly, caused a dose-dependent inhibition of intestinal motility. Clonidine given by the intracisternal route appeared to be more effective than by the intracerebroventricular route. Centrally administered clonidine was antagonized by prior subcutaneous administration of yohimbine. The antagonism was related to the doses of yohimbine given. Subcutaneously administered morphine caused a dose-dependent inhibition of intestinal motility and this effect was antagonized by prior subcutaneous administration of yohimbine. However, administration of yohimbine centrally, either intracisternally or intracerebroventricularly, did not affect the intestinal inhibitory action of morphine. On the other hand, morphine injected centrally, either intracisternally or intracerebroventricularly, dose-dependently inhibited the motility of the intestine; such inhibitory action was antagonized by prior subcutaneous administration of yohimbine. The present study suggests that clonidine inhibits intestinal motility at both central and peripheral sites through alpha 2-adrenoceptors. Morphine also inhibits intestinal motility by both central and peripheral mechanisms but it appears that yohimbine only modifies the peripheral aspect of morphine's action.