SELECTIVITY OF LG50643 FOR POSTJUNCTIONAL MUSCARINIC-RECEPTOR SUBTYPE IN THE GUINEA-PIG TRACHEA

被引:5
作者
DAGOSTINO, G [1 ]
RENZETTI, AR [1 ]
ZONTA, F [1 ]
SUBISSI, A [1 ]
机构
[1] LAB GUIDOTTI SPA,DEPT PHARMACOL,I-56122 SAN PIERO A GRADO,ITALY
关键词
D O I
10.1111/j.2042-7158.1994.tb03807.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of (+/-)-LG50643, a new N-quaternary tropinic ester of phenylcyclohexene carboxylic acid, endowed with a potent antimuscarinic activity, have been investigated on muscarinic receptor-mediated responses of the guinea-pig trachea to electrical field stimulation. An isolated preparation which allows the simultaneous measurement of tritiated acetylcholine release (prejunctional effect) and smooth muscle contraction (postjunctional effect) was used. The guinea-pig epithelium-deprived trachea was stimulated with 500 pulses (20 Hz, 1 ms, 9 V for 5 s, 30 s apart) in the presence of indomethacin (1 mum). Three successive pre- and postjunctional responses were observed. The potencies (-logEC50) of (+/-)-LG50643 for pre- and postjunctional muscarinic receptors were determined and compared with those of selective muscarinic antagonists. In addition, the affinity values of (+/-)-LG50643 for muscarinic-receptor subtypes were determined in radioligand binding experiments in cerebral cortex, heart and salivary glands of rat as target tissues for M1, M2 and M3 receptors, respectively. The results obtained in both functional and binding assays indicate (+/-)-LG50643 is a potent and selective antagonist for the M3-receptor subtype.
引用
收藏
页码:332 / 336
页数:5
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