Stereoselectivity of satropane, a novel tropane analog, on iris muscarinic receptor activation and intraocular hypotension

Autor: Pei-li Zheng, Li-Min Yang, Yong-Yao Cui, Pi-jing Wei, Qiu-shi Ren, Yin-Yao Niu, Liang Zhu, Yang Lu, Hao Wang, Hong-Zhuan Chen
Rok vydání: 2008
Předmět:
Zdroj: Acta Pharmacologica Sinica. 29:177-184
ISSN: 1745-7254
1671-4083
DOI: 10.1111/j.1745-7254.2008.00722.x
Popis: Aim: To study the stereoselectivity of satropane (3-paramethylbenzene sulfonyloxy-6-acetoxy tropane), a novel tropane analog, on iris muscarinic receptor activation and intraocular hypotension. Methods: The assays for radioligand-receptor binding, the contractile responses of isolated iris muscle, the miosis response, and the intraocular hypotension of the enantiomers of satropane were investigated. Results: In the binding analysis, S (–)satropane (lesatropane) completely competed against the [ 3 H]quinuclydinyl benzilate-labeled ligand at muscarinic receptors in the iris muscle, whereas R (+)satropane failed to completely compete. In an isolated iris contractile assay, R,S (±)satropane and S (–)satropane produced a concentration-dependent contractile response with similar efficacy and potency to that of carbachol. R (+)satropane did not induce any contractile response. In the pupil diameter measurement assay in vivo , S (–)satropane induced miosis much more effectively than pilocarpine, while R (+)satropane failed to produce any miosis. In the water loading-induced and methylcellulose-induced ocular hypertensive models, S (–)satropane, but not R (+)satropane, significantly suppressed intraocular pressure at a much lower concentration than pilocarpine. Conclusion: The agonistic and hypotensive properties of satropane on rabbit eyes are stereoselective, with the S (–)isomer being its active form.
Databáze: OpenAIRE
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