Takeuchi K, Goto K, Kasuya Y
Jpn J Pharmacol. 1986 Jul;41(3):325-34. doi: 10.1254/jjp.41.325.
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.
研究了新合成的5-咪唑啉衍生物对大鼠正常和去神经支配输精管中去甲肾上腺素剂量-反应关系的影响。三种衍生物（K-3827、K-4011和K-4300）具有α-拮抗作用，其效力与妥拉唑啉相似。这些衍生物和目前已知的α-拮抗剂（妥拉唑啉、酚妥拉明和哌唑嗪，但不包括育亨宾）在去神经支配组织中的pA2值略高于正常组织，但差异显著。所有咪唑啉衍生物和α-拮抗剂均可使正常输精管对去甲肾上腺素的最大反应增加。然而，在去神经支配组织中，K-3827、K-4011和α-拮抗剂仅使去甲肾上腺素的剂量-反应曲线右移，而不增加最大反应，即相对纯粹的α-拮抗作用。相比之下，另外3种咪唑啉衍生物，既无α-激动作用也无拮抗作用的K-4299和K-6342以及K-4300，即使在去神经支配后也能增加对去甲肾上腺素的最大反应。它们的作用是非特异性的，因为它们也能增强正常和去神经支配组织中乙酰胆碱诱导的收缩。这3种咪唑啉衍生物拮抗地尔硫卓的作用。讨论了咪唑啉衍生物和α-拮抗剂的作用与去神经支配的关系，并从钙转运的角度分析了3种咪唑啉衍生物的药物增强作用。
