SDZ NVI 085，一种兼具5-HT2A受体拮抗剂特性的α1A肾上腺素能受体激动剂。

SDZ NVI 085, an alpha 1A-adrenoceptor agonist with 5-HT2A receptor antagonist properties.

作者信息

Lachnit W G, Ford A P, Clarke D E

机构信息

Roche Bioscience, Palo Alto, CA 94304, USA.

出版信息

Eur J Pharmacol. 1996 Feb 15;297(1-2):83-6. doi: 10.1016/0014-2999(95)00850-0.

DOI:10.1016/0014-2999(95)00850-0

PMID:8851170

Abstract

(+/-)-SDZ NVI 085 (3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9- methylthio-2H-naphth [2,3-b]-1,4-oxazine hydrochloride), an alpha 1-adrenoceptor agonist, produced a concentration-dependent relaxation (pIC50 of 7.2 +/- 0.1) in the isolated caudal artery of rat precontracted with serotonin (5-hydroxytryptamine, 5-HT, 1 microM). (+/-)- SDZ NVI 085 had no effect upon caudal arteries precontracted with vasopressin or U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha). In other studies, (+/-)-SDZ NVI 085 shifted 5-HT concentration-effect curves to the right, in a concentration-dependent manner, and Schild regression gave a pA2 estimate of 8.0 (slope of 1.0). Experiments using pharmacological resultant analysis indicated a syntopic interaction of (+/-)-SDZ NVI 085 with ketanserin (a 5-HT2 receptor antagonist) toward 5-HT-induced contractions. It is concluded that (+/-)-SDZ NVI 085 behaves as a reversible competitive 5-HT2A receptor antagonist, a property which may be of importance regarding its pharmacological effects in vivo.

摘要

（±）-SDZ NVI 085（3,4,4a,5,10,10a-六氢-6-甲氧基-4-甲基-9-甲硫基-2H-萘并[2,3-b]-1,4-恶嗪盐酸盐），一种α1肾上腺素能受体激动剂，在与5-羟色胺（5-羟色胺，5-HT，1微摩尔）预收缩的大鼠离体尾动脉中产生浓度依赖性舒张作用（pIC50为7.2±0.1）。（±）-SDZ NVI 085对用加压素或U46619（9,11-二脱氧-11α,9α-环氧甲撑前列腺素F2α）预收缩的尾动脉无作用。在其他研究中，（±）-SDZ NVI 085以浓度依赖性方式使5-HT浓度-效应曲线右移，Schild回归得出pA2估计值为8.0（斜率为1.0）。使用药理学结果分析的实验表明，（±）-SDZ NVI 085与酮色林（一种5-HT2受体拮抗剂）对5-HT诱导的收缩存在同位相互作用。结论是，（±）-SDZ NVI 085表现为一种可逆竞争性5-HT2A受体拮抗剂，这一特性可能与其体内药理作用有关。