Analysis of new imidazoline derivative-induced increase in the maximum response to norepinephrine in the rat vas deferens.
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 alpha-antagonistic action, the potency of which was similar to that of tolazoline. The pA2 values of these derivatives and currently known alpha-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 alpha-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 alpha-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 alpha-antagonism. In contrast, the other 3 imidazoline derivatives, K-4299 and K-6342 which exhibited neither alpha-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 alpha-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.
D000109:Acetylcholine / Q000008:administration & dosage; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004110:Diltiazem / Q000037:antagonists & inhibitors; D004357:Drug Synergism; D007093:Imidazoles / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D004110:Diltiazem; D000109:Acetylcholine; D009638:Norepinephrine