New Research Areas Glaucoma

While FP prostaglandin analog esters currently dominate the therapeutic scene for treatment of ocular hypertension and glaucoma, investigators are keen to discover new drugs that may supplant the prostaglandins and/or be combined with the prostaglandins in the future. On the horizon are some new ocular hypotensive agents with a variety of mechanisms of action. These include protein kinase inhibitors such as rho kinase inhibitors (e.g., Y-27632)71; myosin-II ATPase inhibitor (blebbistatin)72; 5HT2 receptor agonists (a-methyl-5HT; AL-34662) ; adenosine agonists (2-alkynyladenosine); diadenosine polyphosphates73; calcium antagonists (nivaldepine and flunarizine)74; an angiotensin AT1 receptor antagonist (CS-0 88)75 ; 5HT1A agonists76; melatonin agonists74; dopamine agonists (PD128907, 3-PPP, CHF1035, and CHF10 24)77; agents that degrade glyocosaminoglycans (AL-3037A)78; cannabinoid agonists79; natriuretic peptides80; marine macrolides (e.g., latrunculins and bumetamide)2; chloride transport inhibitors (ethacrynic acid)82; and various prostanoids of DP- and TP-class. Additional compounds of undefined mechanisms that appear to lower IOP in various animal models are listed in Table 2. However, due to major species differences in the ocular hypotensive activities of these agents, it is unclear which if any will become bona fide drugs to treat ocular hypertension and glaucoma in the future.



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