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

作　　者：Liang ZHU Li-min YANG Yong-yao CUI Pei-li ZHENG Yin-yao NIU Hao WANG Yang LU Qiu-shi REN Pi-jing WEI Hong-zhuan CHEN 

机构地区：[1]Department of Pharmacy, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China [2]Institute For Laser Medicine and Bio-photonics, Shanghai Jiao Tong University, Shanghai 200040, China

出　　处：《Acta Pharmacologica Sinica》2008年第2期177-184,共8页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China （No 30472012）, the Major State Basic Research Development Program of China （No 2005CB724302）, and the Key Project of Shanghai Municipal Science and Technology Commission （No 034319230 and 03JC14064）.

摘　　要：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 [^3H]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 ago- nistic and hypotensive properties of satropane on rabbit eyes are stereoselective, with the S（-）isomer being its active form.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 [^3H]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 ago- nistic and hypotensive properties of satropane on rabbit eyes are stereoselective, with the S（-）isomer being its active form.

关 键 词：muscarinic receptor chiral tropane analog satropane lesatropane 

分 类 号：R77[医药卫生—眼科]