Novel agonists of melatonin receptors as promising hypotensive and neuroprotective agents for therapy of glaucoma
Melatonin is a pineal hormone that has a capacity to lower intraocular pressure; it exhibits neuroprotective and antioxidant properties that make it possible to use melatonin in the therapy of glaucoma. Analogs of melatonin having affinity to melatonin receptors are promising candidates for application as antiglaucomatous drugs. Chemical modification of the melatonin structure can in-crease efficiency, bioavailability and selectivity of these analogs. We have designed and synthe-sized a number of new 2-oxindole derivatives – ligands of melatonin MT3 subtype receptors that displayed ability to lower intraocular pressure in normotensive rabbits and high antioxidant activity against hydroxyl radical and superoxide anion-radical. The antioxidant activity of new ligands was several times higher than one of melatonin that makes them prospective therapeutic tools for the diseases that include oxidative stress. The maximal hypotensive effect of analogs was comparable to that of melatonin itself but prolonged. Combination of these properties gives an opportunity of using the presented melatonin analogs in complex therapy of glaucoma.