Carratù M R, Navarra P, De Serio A, Serio M, Preziosi P, Mitolo-Chieppa D
Institute of Pharmacology, University of Bari, School of Medicine, Italy.
Fundam Clin Pharmacol. 1992;6(7):301-7. doi: 10.1111/j.1472-8206.1992.tb00124.x.
The effects of idazoxan (IDZ) and its stereoisomers were compared to that of a classical alpha 2-antagonist, yohimbine (YOH), on para-aminoclonidine (PAC)- and norepinephrine (NE)-mediated inhibition of the twitch response evoked in the mouse vas deferens by low-frequency (0.1 Hz) field stimulation. (+/-)-IDZ and (+)-IDZ antagonized the inhibitory effects of PAC, (+)-IDZ being twice as potent as (+/-)-IDZ; in contrast, antagonism by (-)-IDZ failed to meet Schild criteria for a competitive mechanism. YOH completely reversed the inhibition of twitch response induced by NE, but not that induced by PAC; in the latter case, residual inhibition was almost fully reversed by (+)-IDZ and to a lesser extent by (+/-)-IDZ, while (-)-IDZ proved ineffective. These results provide pharmacological evidence of alpha 2-receptor heterogeneity at the vas deferens level. A possible additional mechanism involving imidazoline binding sites is discussed.
将咪唑克生（IDZ）及其立体异构体的作用与经典α2拮抗剂育亨宾（YOH）的作用进行比较，观察它们对在小鼠输精管中由低频（0.1Hz）场刺激诱发的抽搐反应的对氨基可乐定（PAC）和去甲肾上腺素（NE）介导的抑制作用。（±）-IDZ和（+）-IDZ拮抗PAC的抑制作用，（+）-IDZ的效力是（±）-IDZ的两倍；相比之下，（-）-IDZ的拮抗作用不符合竞争性机制的希尔德标准。YOH完全逆转NE诱导的抽搐反应抑制，但不能逆转PAC诱导的抑制；在后一种情况下，残余抑制几乎被（+）-IDZ完全逆转，（±）-IDZ在较小程度上逆转，而（-）-IDZ无效。这些结果提供了输精管水平上α2受体异质性的药理学证据。讨论了涉及咪唑啉结合位点的可能的附加机制。
