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  • Title: Steric structure activity relationships of various adrenergic agonists: ocular and systemic effects.
    Author: Rowland JM, Potter DE.
    Journal: Curr Eye Res; 1981; 1(1):25-35. PubMed ID: 6117417.
    Abstract:
    Dextrorotatory (d) forms of adrenergic drugs are known to be much less active than the levo (l) forms in effecting classical adrenergically mediated responses (alpha, beta 1, beta 2) in metabolic organs and cardiovascular tissues. Adrenoceptor intrinsic activity and affinity, enzymatic inactivation and neuronal uptake are all known to be relatively selective for the l-forms. It is known, however, that the d-isomers of certain agonists, such as isoproterenol, are as effective or even more effective ocular hypotensive agents than their respective l-forms or the racemates (dl) in rabbits. We tested the d- and l-isomers of epinephrine (alpha, beta 1, beta 2), norepinephrine (alpha, beta 1), phenylephrine (alpha 1), isoproterenol (beta 1, beta 2) and soterenol (alpha, beta 2) for their comparative effects after topical administration on intraocular pressure (IOP), pupil diameter (PD), arterial blood pressure (ABP) (after both topical and i.v. administration), aqueous cAMP, and aqueous and plasma lactate and glucose in the normotensive rabbit model. The results with ABP and concomitant changes in plasma biochemical correlates normally associated with adrenergic mechanisms were consistent with well established theory of stereospecificity. Data from ocular parameters, however, suggest that d-isomers of adrenergic agents evoke ocular responses that are divergent from this theory. The relation of ocular and systemic pressure responses with their respective biochemical correlates suggests that some d-isomers of adrenergic stimulants may be acting as partial agonists.
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