Inhibitory effects of ketamine on the isolated uteri of the rat: evidence for the mechanism of action.

The inhibitory effect of ketamine on the agonist-induced contraction of isolated rat uteri was compared with that of papaverine and verapamil. Under similar experimental conditions papaverine and verapamil were found to be more potent than ketamine. When preparations were preincubated for 20 min with either ketamine (3 X 10(-5) to 10(-3) M) or papaverine (10(-6) to 10(-5) M), a noncompetitive antagonism was observed against oxytocin with pD'2 values of 3.67 +/- 0.07 and 5.13 +/- 0.10, respectively. A noncompetitive form of antagonism was also observed by papaverine against BaCl2 with pD'2 values of 4.59 +/- 0.15, while ketamine produced competitive antagonism with a pA2 value of 4.68 +/- 0.12. It was also demonstrated that all three inhibitory drugs interfere competitively with Ca2+ on the rat uteri. However, ketamine was shown to be less potent than verapamil and papaverine in antagonizing the effects owing to an increased Ca2+ concentration in the medium. These results are consistent with previous publications that ketamine has a papaverinelike effect on the rat uteri and suggest that the relaxation promoted in this preparation is due, at least in part, to blockade of the Ca2+ translocation processes.