Muramatsu I, Yamanaka K, Kigoshi S
Department of Pharmacology, Fukui Medical School, Japan.
Jpn J Pharmacol. 1991 Mar;55(3):391-8. doi: 10.1254/jjp.55.391.
The pharmacological profile of a new alpha-adrenoceptor antagonist, KT-611 (naftopidil), was studied in vitro. In the dog mesenteric and carotid arteries and in the rabbit, guinea pig and rat thoracic aortae, KT-611 competitively inhibited alpha 1-adrenoceptor-mediated contractions induced by noradrenaline with pA2 values ranging from 6.73 to 8.15. KT-611 also inhibited the postjunctional alpha 2-adrenoceptor-mediated contractions in the dog saphenous vein (pA2 = 6.77) or dog basilar artery. However, the responses mediated through prejunctional alpha 2-adrenoceptors (rat vas deferens), beta-adrenoceptors (rat atria), muscarinic receptors (guinea pig ileum) and 5-HT2 receptors (dog mesenteric artery) were little affected by KT-611. KT-611 also inhibited the sympathetic adrenergic contraction evoked by electrical transmural stimulation in the dog mesenteric artery, and the inhibition was not relieved upon repetitive washing for 1 hour with the drug-free solution. 3H-prazosin and 3H-clonidine binding to the rat cortex membranes was inhibited by KT-611 with pKi values of 7.69 and 5.75, respectively. These results suggest that KT-611 is an alpha 1-adrenoceptor antagonist with a weak antagonistic activity to postjunctional alpha 2-adrenoceptors.
在体外研究了新型α-肾上腺素能受体拮抗剂KT-611（萘哌地尔）的药理学特性。在犬肠系膜动脉和颈动脉以及兔、豚鼠和大鼠的胸主动脉中，KT-611竞争性抑制去甲肾上腺素诱导的α1-肾上腺素能受体介导的收缩，其pA2值范围为6.73至8.15。KT-611还抑制犬隐静脉（pA2 = 6.77）或犬基底动脉中节后α2-肾上腺素能受体介导的收缩。然而，KT-611对通过节前α2-肾上腺素能受体（大鼠输精管）、β-肾上腺素能受体（大鼠心房）、毒蕈碱受体（豚鼠回肠）和5-HT2受体（犬肠系膜动脉）介导的反应影响很小。KT-611还抑制犬肠系膜动脉经皮电刺激诱发的交感肾上腺素能收缩，且用无药溶液反复冲洗1小时后该抑制作用未解除。KT-611抑制3H-哌唑嗪和3H-可乐定与大鼠皮层膜的结合，其pKi值分别为7.69和5.75。这些结果表明，KT-611是一种α1-肾上腺素能受体拮抗剂，对节后α2-肾上腺素能受体具有较弱的拮抗活性。
