@article{APS4249,
author = {Liang Zhu and Li-min Yang and Yong-yao Cui and Pei-li Zheng and Yin-yao Niu and Hao Wang and Yang Lu and Qiu-shi Ren and Pi-jing Wei and Hong-zhuan Chen},
title = {Stereoselectivity of satropane, a novel tropane analog, on iris muscarinic receptor activation and intraocular hypotension},
journal = {Acta Pharmacologica Sinica},
volume = {29},
number = {2},
year = {2016},
keywords = {},
abstract = {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 agonistic and hypotensive properties of satropane on rabbit eyes are stereoselective, with the S(–)isomer being its active form.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4249}
}