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


CONCLUSIONS
The agonistic and hypotensive properties of satropane on rabbit eyes are stereoselective, with the S(-)isomer being its active form.
Zhu
Liang
L
Department of Pharmacy, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Yang
Li-min
LM
Cui
Yong-yao
YY
Zheng
Pei-li
PL
Niu
Yin-yao
YY
Wang
Hao
H
Lu
Yang
Y
Ren
Qiu-shi
QS
Wei
Pi-jing
PJ
Chen
Hong-zhuan
HZ
D000818:Animals; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects*; D018721:Muscarinic Agonists / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D015814:Ocular Hypotension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011680:Pupil / Q000187:drug effects; D011817:Rabbits; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013237:Stereoisomerism; D014326:Tropanes / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D014326:Tropanes; C535253:satropane