Exploring the potential for subtype-selective muscarinic agonists in glaucoma

Pilocarpine has been used to lower intraocular pressure (IOP) in glaucoma p atients for more than 100 years. Since the identification of five muscarini c receptor subtypes, there has been an interest in separating the TOP-lower ing effects from the ocular side effects of pupil constriction and lens acc ommodation. However, all these actions seem to be mediated by the M-3 recep tor. A novel muscarinic receptor agonist, AGN 199170, that has no activity on the M-3 subtype was compared to pilocarpine in a monkey glaucoma model. This compound lowered IOP suggesting that muscarinic agonists targeted at m uscarinic receptors other than the M-3 subtype may be able to selectively l ower TOP. (C) 2001 Elsevier Science Inc. All rights reserved.