Interaction of SSR161421, a novel specific adenosine A3 receptor antagonist with adenosine A3 receptor agonists both in vitro and in vivo

被引：2

作者：

Mikus, Endre G. ^{[1
]}

Boer, Kinga ^{[1
]}

Timari, Geza ^{[1
]}

Urban-Szabo, Katalin ^{[1
]}

Kapui, Zoltan ^{[1
]}

Szeredi, Judit ^{[1
]}

Gerber, Katalin ^{[1
]}

Szabo, Tibor ^{[1
]}

Batori, Sandor ^{[1
]}

Finet, Michel ^{[1
]}

Aranyi, Peter ^{[1
]}

Galzin, Anne-Marie ^{[1
]}

机构：

[1] Sanofi Co Ltd, H-1045 Budapest, Hungary

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2013年 / 699卷 / 1-3期

关键词：

Human adenosine A(3) receptors; Adenosine A(3) receptor antagonist; Ear oedema; Histamine release; FUNCTIONAL-CHARACTERIZATION; RELEASE;

D O I：

10.1016/j.ejphar.2012.11.046

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 (CI-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 (ED50=2.0 mg/kg) and the CI-IB-MECA evoked plasma extravasation (ID50=2.9 mg/kg) and oedema formation (ID50=4.6 mg/kg) in mouse ear. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：62 / 66

页数：5

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