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Comparison of agonistic and antagonistic actions of guanabenz and guanfacin on alpha 1 and alpha 2-adrenoceptors in isolated smooth muscles.

The effects of guanabenz, guanfacine and clonidine on alpha-adrenoceptors were investigated in isolated rat vas deferens and rabbit aortic strip. All 3 drugs at low concentrations (10(-9)-10(-8) M) caused inhibition of twitch responses of the rat vas deferens induced by nerve stimulation. These effects were competitively antagonized by yohimbine. Guanfacine and clonidine at relatively high concentrations (10(-6)-10(-4) M) produced contractions of the rat vas deferens which were antagonized by prazosin. These contractile responses were not much affected by denervation. Prazosin-sensitive contractions by guanfacine and clonidine were also observed in the rabbit aortic strip, which were not affected by reserpine pretreatment. In both tissues, the intrinsic activity of guanfacine was almost identical to that of norepinephrine, whereas that of clonidine was less than one half. Guanabenz and clonidine showed a competitive antagonistic effect against norepinephrine and phenylephrine in both the rat vas deferens and rabbit aorta, the antagonisms being similar in potency. The results indicate that all 3 drugs are potent agonists on the presynaptic alpha 2-adrenoceptor. In contrast, on the postsynaptic alpha 1-adrenoceptor, guanfacine and guanabenz showed only agonistic and antagonistic actions, respectively, whereas clonidine exhibited partial agonistic characteristics.