Analysis of New Imidazoline Derivative-Induced Increase in the Maximum Response to Norepinephrine in the Rat Vas Deferens

抄録

The effects of newly synthesized 5-imidazoline derivatives on the dose-response relationship to norepinephrine were investigated in the normal and denervated vasa deferentia of the rat. Three derivatives (K-3827, K-4011 and K-4300) exerted α-antagonistic action, the potency of which was similar to that of tolazoline. The pA₂ values of these derivatives and currently known α-antagonists (tolazoline, phentolamine and prazosin, but not yohimbine) in the denervated tissue were slightly but significantly larger than those in the normal tissue. All imidazoline derivatives and α-antagonists produced an increase in the maximum response to norepinephrine in the normal vas deferens. In the denervated tissue, however, K-3827, K-4011 and α-antagonists caused only a rightward shift of the dose-response curve to norepinephrine, but not an increase in the maximum response, i.e., relatively pure α-antagonism. In contrast, the other 3 imidazoline derivatives, K-4299 and K-6342 which exhibited neither α-agonistic nor antagonistic action and K-4300, increased the maximum response to norepinephrine even after denervation. Their effects were nonspecific in that they also potentiated acetylcholine-induced contractions in both normal and denervated tissues. These 3 imidazoline derivatives antagonized the action of diltiazem. The effects of imidazoline derivatives and α-antagonists were discussed in relation to those of denervation, and the drug enhancement by 3 imidazoline derivatives was analyzed from the viewpoint of calcium movement.