The intraocular pressure and the pupillary responses of conscious rabbits to racemic erythro-alpha-methylnorepinephrine.
The intraocular pressure and the pupillary responses in conscious rabbits to racemic erythro-alpha-methylnorepinephrine (alpha MeNE) have been investigated and its activity compared to L-norepinephrine (NE). Aqueous solutions of alpha MeNE applied topically caused dose-dependent decreases of intraocular pressure and of pupil dilatation. The maximal intraocular pressure response to alpha MeNE exceeded that to NE, and the sensitivity of the intraocular pressure response exceeded that to NE by 10-20 times. The onset of the decrease in intraocular pressure to alpha MeNE was rapid and contrasted to the slow onset of the intraocular hypotensive response to NE. Preganglionic cervical sympathotomy did not effect the intraocular pressure and the pupillary responses to either alpha MeNE or NE. Superior cervical ganglionectomy induced supersensitivity to NE but not to alpha MeNE. Studies using alpha 1, alpha 2, and beta adrenoceptor antagonists indicated that the intraocular pressure responses to alpha MeNE were mediated primarily by alpha 2 and beta adrenoceptors whereas the responses to NE were mediated primarily by alpha 1 adrenoceptors. The observations are discussed in the light of recent data of the affinities of alpha MeNE and NE to alpha 1, alpha 2, and beta adrenoceptors. The high potency of alpha MeNE compared to NE in decreasing intraocular pressure and in dilating the pupil does not correlate with their binding affinities to alpha and beta adrenoceptors. The observations support an alternative explanation that the differences in the potencies of alpha MeNE and NE are due to differences in rates of inactivation of the two compounds in the adrenergic neurone.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D007536:Isomerism; D008297:Male; D008771:Nordefrin / Q000494:pharmacology*; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects*; D011817:Rabbits; D013562:Sympathectomy; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D008771:Nordefrin; D009638:Norepinephrine