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

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.

• Authors: 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
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 29 Issue 2 Pg. 177-84 (Feb 2008) ISSN: 1671-4083 [Print] United States
• PMID: 18215346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Muscarinic Agonists
• Receptors, Muscarinic
• Tropanes
• satropane

Topics

• Animals
• In Vitro Techniques
• Iris (drug effects)
• Muscarinic Agonists (chemistry, pharmacology, therapeutic use)
• Ocular Hypotension (chemically induced, drug therapy, physiopathology)
• Pupil (drug effects)
• Rabbits
• Radioligand Assay
• Receptors, Muscarinic (drug effects)
• Stereoisomerism
• Tropanes (chemistry, pharmacology, therapeutic use)