DAU 6285：一种新型的假定5-羟色胺4受体拮抗剂。

DAU 6285: a novel antagonist at the putative 5-HT4 receptor.

作者信息

Schiavone A, Giraldo E, Giudici L, Turconi M, Sagrada A

机构信息

Department of Pharmacology, Boehringer Ingelheim Italia, (Istituto De Angeli s.p.A.), Milano.

出版信息

Life Sci. 1992;51(8):583-92. doi: 10.1016/0024-3205(92)90227-g.

DOI:10.1016/0024-3205(92)90227-g

PMID:1640809

Abstract

The antagonistic properties of DAU 6285, an azabicycloalkyl benzimidazolone derivative, at putative 5-hydroxytryptamine4 (5-HT4) receptors were investigated in in vitro preparations of guinea-pig ileum and human atrium, in comparison to ICS 205-930. DAU 6285 behaved as a competitive antagonist in all the preparations examined. Its affinity (pA2) ranged between 6.50 and 7.12 in the test models considered. The affinity of ICS 205-930 was 2-3 fold lower. At variance with ICS 205-930, DAU 6285 displayed a weak affinity for 5-HT3 receptors (pKi = 6.1, rat cortex; pA2 less than 5, guinea-pig ileum). In the guinea-pig ileum, DAU 6285 (10 microM) did not exert antimuscarinic, antihistaminic, antinicotinic or myolytic activity. Moreover, it did not bind to other 5-HT receptor subtypes, or to adrenergic, dopaminergic, benzodiazepine, nicotine, GABA receptors. DAU 6285 may represent a suitable tool for studies in the field of 5-HT4 receptors.

摘要

与ICS 205-930相比，在豚鼠回肠和人心房的体外制剂中研究了氮杂双环烷基苯并咪唑酮衍生物DAU 6285对假定的5-羟色胺4（5-HT4）受体的拮抗特性。在所有检测的制剂中，DAU 6285表现为竞争性拮抗剂。在所考虑的测试模型中，其亲和力（pA2）在6.50至7.12之间。ICS 205-930的亲和力低2至3倍。与ICS 205-930不同，DAU 6285对5-HT3受体表现出较弱的亲和力（pKi = 6.1，大鼠皮层；pA2小于5，豚鼠回肠）。在豚鼠回肠中，DAU 6285（10 microM）不具有抗毒蕈碱、抗组胺、抗烟碱或溶肌活性。此外，它不与其他5-HT受体亚型结合，也不与肾上腺素能、多巴胺能、苯二氮䓬、烟碱、GABA受体结合。DAU 6285可能是5-HT4受体领域研究的合适工具。