Ocular hypotension in the rabbit. Receptor mechanisms of pirbuterol and nylidrin.
Pirbuterol and nylidrin, both purported sympathomimetic amines, reduced intraocular pressure (IOP) when given topically (50 microliter, 0.1%) to albino rabbits. Pirbuterol increased the cyclic-AMP concentration in aqueous humor by a factor of 3.25, while nylidrin had no effect on aqueous cyclic-AMP nor on adenylate cyclase activity of iris-ciliary body membranes assayed in vitro. Studies of the receptor affinity of pirbuterol, timolol and nylidrin were carried out on iris-ciliary body membranes by competition binding with radioactive ligands. Four ligands were used that appear to label separate subpopulations of adrenergic receptors; dihydroalprenolol (beta-receptors), WB-4101 (alpha 1-receptors) prazosin (alpha 1-receptor subpopulation) and yohimbine (alpha 2-receptors). Pirbuterol and timolol showed exclusive selectivity for beta-receptors with high affinities (Kd 12.6 and 0.48 nM, respectively) compared with other adrenergic receptor populations in iris-ciliary body. Nylidrin had high affinities for beta-receptors (Kd 22 nM) and for the subpopulation of alpha 1-receptors labelled by prazosin (Kd 6.5 nM), but showed 100-fold lower affinity and complex binding characteristics to the two other classes of alpha-adrenergic receptor sites labelled by WB-4101 and yohimbine, respectively. The results show that pirbuterol and timolol are highly beta-receptor selective and that hypotensive responses to these drugs are not mediated by the other classes of alpha-adrenergic receptor determined in this study. However, the hypotensive response to nylidrin may be related to its prazosin-like (alpha 1-receptor) antagonist properties with additional activity at beta-receptors.
Mittag
T W
TW
Tormay
A
A
Messenger
M
M
Podos
S M
SM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001667:Binding, Competitive; D002924:Ciliary Body / Q000187:drug effects / Q000201:enzymology / Q000294:innervation*; D000242:Cyclic AMP / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D007498:Iris / Q000187:drug effects / Q000201:enzymology / Q000294:innervation*; D009756:Nylidrin / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013999:Timolol / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D009756:Nylidrin; D013999:Timolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C009118:pirbuterol