Acta Pharmacologica Sinica 2008 February; 29 (2): 177-184; doi: 10.1111/j.1745-7254.2008.00722.x

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.

Keywords: muscarinic receptor; chiral; tropane analog; satropane; lesatropane