Dopaminoceptor agonists can lower intraocular pressure (IOP) in rabbits and monkeys. This research project is designed to investigate the site(s) and mechanisms(s) by which these drugs produce ocular hypotension. Representatives of four classes of dopamine agonists (ergolines, phenylethylamines, aminotetralins, aporphines) will be compared for their acute and chronic effects on aqueous humor dynamics and iris function. Relatively selective dopaminocepter antagonists (sulpiride, domperidone) and specific biochemical correlates (cyclic AMP) will be used to identify the subpopulation of dopaminoceptor (DA1 or DA2) involved in the ocular responses. Surgical sympathectomy in rabbits and the superior cervical ganglion preparation in the cat will be used to establish whether the mode of action of these compounds involves a prejunctional (neuronal) component. An IOP recovery rate method and a fluorophotometric procedure will be used to determine the primary parameter of aqueous flow that is affected by these drugs. Results from this study should enhance the level of knowledge regarding dopaminoceptors and their role in regulating ocular hydrodynamics. Moreover, this project will demonstrate whether or not dopaminoceptors constitute potential targets for a new class of antiglaucoma drugs.
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