Pharmacological studies on supersensitization. VII. Inhibitory effect of dibenamine on cocaine-induced supersensitivity of isolated vas deferens of guinea pig

Effects of dibenamine on cocaine-induced supersensitivity of isolated vas deferens of guinea pig were examined. Dibenamine at 1.0 x 10(-7)-1.0 x 10(-5) M attenuated the degree of cocaine-induced increase in sensitivity to acetylcholine without any effect on acetylcholine-contraction. The degree of dibenamine-induced inhibition was dependent on the concentration of dibenamine and inversely related to the concentration of cocaine. Dibenamine at the concentration capable of inhibiting the contractile response to norepinephrine did not affect the degree of the increase in sensitivity to norepinephrine induced by cocaine. Dibenamine diminished the degree of cocaine-induced increase in sensitivity to potassium in standard Tyrode solution and that in maximum response to calcium in partially depolarized vas deferens. Dibenamine at the concentration of 3.2 x 10(-7) M did not affect acetylcholine-contractions and attenuated potassium-contractions of the preparations exposed 5 min to calcium-free Tyrode solution, but the degree of cocaine-induced potentiation of contractile response in calcium-free Tyrode solution was not affected by dibenamine. These results suggest that cocaine-induced increase in calcium influx from extracellular fluid is selectively inhibited by dibenamine.