SSR161421 与腺嘌呤 A（3）受体激动剂在体外和体内均相互作用，是一种新型的特异性腺嘌呤 A（3）受体拮抗剂。

Interaction of SSR161421, a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo.

机构信息

Sanofi Co. Ltd., H-1045 Budapest Tó utca 1-5, Hungary.

出版信息

Eur J Pharmacol. 2013 Jan 15;699(1-3):62-6. doi: 10.1016/j.ejphar.2012.11.046. Epub 2012 Dec 5.

DOI:10.1016/j.ejphar.2012.11.046

PMID:23219789

Abstract

A novel adenosine A(3) receptor antagonist (SSR161421) was characterized by both receptor binding assays and pharmacological tests. Binding studies on cloned human adenosine receptors showed that SSR161421 has high affinity for adenosine hA(3) receptors (K(i)=0.37 nM) with at least 1000-fold selectivity compared to hA(1), hA(2A) and hA(2B) receptors. The receptor antagonist nature of SSR161421 was determined in a functional study on Chinese hamster ovarian cells (CHO) cells expressing human adenosine A(3) receptors. SSR161421 competitively antagonized the effect of 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (Cl-IB-MECA) on cAMP production with a pA2 value in a luciferase reporter gene construct. In mice, intravenously administered SSR161421 inhibited the N6-(4-aminobenzyl)-adenosine-5'-N-methyl-uronamide dihydrochloride (AB-MECA) induced increase in plasma histamine levels (ED(50)=2.0mg/kg) and the Cl-IB-MECA evoked plasma extravasation (ID(50)=2.9 mg/kg) and oedema formation (ID(50)=4.6 mg/kg) in mouse ear.

摘要

一种新型的腺苷 A(3)受体拮抗剂（SSR161421）通过受体结合测定和药理学测试进行了表征。对克隆的人腺苷受体的结合研究表明，SSR161421对人 hA(3)受体具有高亲和力（K(i)=0.37 nM），与 hA(1)、hA(2A)和 hA(2B)受体相比至少具有 1000 倍的选择性。在表达人腺苷 A(3)受体的中国仓鼠卵巢细胞（CHO）细胞的功能研究中，确定了 SSR161421 的受体拮抗剂性质。SSR161421 竞争性拮抗 2-氯-N6-(3-碘苄基）-腺苷-5'-N-甲基甲酰胺（Cl-IB-MECA）对 cAMP 产生的作用，在荧光素酶报告基因构建体中具有 pA2 值。在小鼠中，静脉内给予 SSR161421 抑制 N6-(4-氨基苄基）-腺苷-5'-N-甲基尿苷二盐酸盐（AB-MECA）诱导的血浆组胺水平升高（ED(50)=2.0mg/kg）和 Cl-IB-MECA 诱发的血浆渗出（ID(50)=2.9 mg/kg）和小鼠耳水肿形成（ID(50)=4.6 mg/kg）。