Open AccessStereoselectivity of satropane, a novel tropane analog, on iris muscarinic receptor activation and intraocular hypotension 1
Author(s) -
ZHU Liang,
YANG Limin,
CUI Yongyao,
ZHENG Peili,
NIU Yinyao,
WANG Hao,
LU Yang,
REN Qiushi,
WEI Pijing,
CHEN Hongzhuan
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00722.x
Subject(s) - miosis , pilocarpine , muscarinic acetylcholine receptor , chemistry , stereoselectivity , carbachol , intraocular pressure , pharmacology , tropane , iris (biosensor) , receptor , stereochemistry , biochemistry , biology , medicine , ophthalmology , neuroscience , computer security , computer science , catalysis , biometrics , epilepsy
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.