Alpha-adrenergic antagonists: correlation of the effect on intraocular pressure and on alpha 2-adrenergic receptor binding specificity in the rabbit eye.
Six alpha-adrenergic antagonists, which have a range of selectivities for alpha 1- and alpha 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 alpha 2-adrenoreceptors, as determined by binding to membranes prepared from rabbit iris-ciliary body. A routine assay for alpha 2-adrenoreceptors using [3H]-rauwolscine was developed for this purpose. ICB contained 200-300 fmol (mg protein)-1 alpha 2-adrenoreceptors which represents approximately two-thirds of the total number of alpha-adrenoreceptor sites present in this tissue. All six antagonists bound at alpha 2-adrenergic receptor sites in an apparently simple competitive manner. The Kd for three of the drugs was about 10 nM (rauwolscine, yohimbine, WB-4101) and the Kd for the other three was greater than 3500 nM (prazosin, corynanthine, thymoxamine). However, all six antagonists were effective ocular hypotensive agents when given topically in a 50 microliter dose of 1% (w/v) concentration. The ability of alpha-adrenergic antagonists to lower IOP in the rabbit did not correlate with a single alpha-receptor subtype and appears to involve at least two separate mechanisms, one mediated by alpha 2-adrenergic receptors and one mediated by alpha 1-adrenergic receptors.
Mittag
T W
TW
Tormay
A
A
Severin
C
C
Podos
S M
SM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002924:Ciliary Body / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D007498:Iris / Q000187:drug effects; D008566:Membranes / Q000187:drug effects; D013948:Moxisylyte / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D013948:Moxisylyte; D011224:Prazosin