Cappello B, Greco G, Novellino E, Perissutti E, Santagada V, Silipo C, Vittoria A, Di Carlo R, Meli R, Muccioli G
Dipartimento di Chimica Farmaceutica e Tossicologica dell'Università di Napoli, Italy.
Farmaco. 1993 Jul;48(7):907-18.
A series of benzotriazole derivatives were synthesized and tested in order to determine their activities for muscarinic receptor subtypes (M1, M2 and M3). Binding affinities were measured as KI values by competition against [3H]-N-methylscopolamine in rat cortex, atria and ileum. Pharmacological in vitro tests were performed on isolated tissue preparations (rabbit vas deferens, guinea pig atria and ileum); the compounds showed antimuscarinic activity. The synthesized ligands were characterized by moderate activity; however, some of them displayed interesting selectivity profiles (M2/M1 and M2/M3); particularly, the selectivity exhibited by the benzotriazole derivative 14b was quite similar to that observed for AF-DX 116, a typical M2 specific antagonist.
合成并测试了一系列苯并三唑衍生物，以确定它们对毒蕈碱受体亚型（M1、M2和M3）的活性。通过在大鼠皮层、心房和回肠中与[3H]-N-甲基东莨菪碱竞争，将结合亲和力测定为KI值。对分离的组织制剂（兔输精管、豚鼠心房和回肠）进行了体外药理学测试；这些化合物表现出抗毒蕈碱活性。合成的配体具有中等活性；然而，其中一些表现出有趣的选择性特征（M2/M1和M2/M3）；特别是，苯并三唑衍生物14b表现出的选择性与典型的M2特异性拮抗剂AF-DX 116所观察到的非常相似。
