摘要：

Urapidil (6-{3-[4-(o-methoxyphenyl)-1-piperazinyl]-propylamino}-1,3-dimethyluracil), phentolamine (both 10 8–10 5 M), yohimbine (10 7 M), and clonidine (10 6–10 5 M) competitively antagonized the effect of noradrenaline on postsynaptic α-adrenoceptors in organ bath-suspended rat vas deferens, yielding pA 2 values of 7.02, 7.64, 6.48 and 5.81, respectively, whereas xylazine (BAY 1470) was ineffective as an antagonist. In contrast to clonidine and xylazine, urapidil did not exert α-adrenoceptor agonist properties at the postsynaptic level in this preparation. Stimulation of presynaptic α-adrenoceptors by urapidil, clonidine and xylazine was assessed by inhibition of twitch contractions of the superfused rat vas deferens in response to intramural nerve stimulation. Inhibition of contraction caused by these drugs was reversed by phentolamine and yohimbine, indicating that they were presynaptic in origin. The presynaptic α-adrenoceptor antagonist activity of urapidil and phentolamine was quantitatively determined by studying the effects of increasing concentrations of these compounds on clonidine dose-response curves in the vas deferens after electrical stimulation. The inhibitory effect of clonidine could be competitively blocked by phentolamine (10 7–10 6 M), whereas urapidil (10 53 × 10 4 M) elicited partial agonism on presynaptic α-adrenoceptors which was apparent from the dose-response curves revealing competitive dualism. The pA 2 value for phentolamine and urapidil against clonidine was 7.97 and 5.11, respectively. These results indicate that, with respect to pre- and postsynaptic α-adrenoceptors, the action of urapidil is complex but suggests a primary presynaptic stimulatory site of action at doses similar to those of clinidine, but with an apparent intrinsic activity of 0.52. The α-adrenoceptor blocking potency of urapidil at the postsynaptic site was 4–8 times weaker than that of phentolamine, whereas antagonism at the presynaptic level was negligible.

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