advertisement

Topcon

Abstract #9946 Published in IGR 5-3

A novel and selective 5-HT2 receptor agonist with ocular hypotensive activity: (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano[3,2-e]indole

May JA; Chen HH; Rusinko A; Lynch VM; Sharif NA; McLaughlin MA
Journal of Medicinal Chemistry 2003; 46: 4188-4195


Serotonin 5-HT2 receptor agonists have recently been shown to be effective in lowering intraocular pressure in nonhuman primates and represent a potential new class of antiglaucoma agents. As part of an effort to identify new selective agonists at this receptor, the authors found that (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano[3,2-e]indole (AL-37350A, 11) has high affinity and selectivity (>1000-fold) for the 5-HT2 receptor relative to other 5-HT receptors. More specifically, 11 is a potent agonist at the 5-HT2A receptor (EC50 = 28.6 nm, Emax = 103%) that is comparable to serotonin. Evaluation of 11 in conscious ocular hypertensive cynomolgus monkeys showed this compound to be efficacious in reducing intraocular pressure (IOP; 13.1 mmHg, -37%). Thus, 11 is a potent full agonist with selectivity for the 5-HT2 receptor and is anticipated to serve as a useful tool in exploring the role of the 5-HT2 receptor and its effector system in controlling IOP.

Dr. J.A. May, Medicinal Chemistry Department, Ophthalmic Products Research, Alcon Research Ltd., 6201 South Freeway, Fort Worth, TX 76134, USA. jesse.may@alconlabs.com


Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)



Issue 5-3

Change Issue


advertisement

Topcon