Experimental compounds to lower intraocular pressure.

A need exists for new ocular hypotensive agents that are more efficacious and that have fewer side effects than those now clinically used. Laser-induced glaucoma in monkeys is an excellent model to test potential new drugs that lower intraocular pressure (IOP). A variety of agents that act through secondary messenger systems or via enzymes to lower IOP are being investigated in primates. Several alpha-adrenergic agonists and antagonists are effective ocular hypotensive agents in monkeys and humans. Para-aminoclonidine, an alpha2 agonist, inhibits the transient post-laser rise of IOP in humans. Prostaglandin F2 alpha-1-isopropyl ester significantly reduces IOP when tested in multiple dose fashion in glaucomatous monkey eyes and glaucoma patients. Modified carbonic anhydrase inhibitors, designed to enhance intraocular penetration, reduce IOP in the monkey model and in ocular hypertensive patients in single-dose studies when given topically. Studies show that forskolin and vanadate are less promising agents for glaucoma therapy.