Abstract
Six alpha-adrenergic antagonists, which have a range of selectivities for α 1- and α 2-adrenoreceptor subtypes, were compared with respect to their ability to reduce intraocular pressure (IOP) after topical application to the rabbit eye, and their affinity and selectivity for α 2-adrenoreceptors, as determined by binding to membranes prepared from rabbit iris-ciliary body. A routine assay for α 2-adrenoreceptors using [ 3H]-rauwolscine was developed for this purpose. ICB contained 200–300 fmol (mg protein) −1 α 2-adrenoreceptors which represents approximately two-thirds of the total number of α-adrenoreceptor sites present in this tissue. All six antagonists bound at α 2-adrenergic receptor sites in an apparently simple competitive manner. The K d for three of the drugs was about 10 n m (rauwloscine, yohimbine, WB-4101) and the K d for the other three was > 3500 n m (prazosin, corynanthine, thymoxamine). However, all six antagonists were effective ocular hypotensive agents when given topically in a 50 μl dose of 1% (w/v) concentration. The ability of α-adrenergic antagonists to lower IOP in the rabbit did not correlate with a single α-receptor subtype and appears to involve at least two separate mechanisms, one mediated by α 2-adrenergic receptors and one mediated by α 1-adrenergic receptors.
Published Version
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