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 μl, 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 (β-receptors), WB-4101 (α₁-receptors), prazosin (α₁-receptor subpopulation) and yohimbine (α₂-receptors). Pirbuterol and timolol showed exclusive selectivity for β-receptors with high affinities (K(d) 12.6 and 0.48 nM, respectively) compared with other adrenergic receptor populations in iris-capillary body. Nylidrin had high affinities for β-receptors (K(d) 22 nM) and for the subpopulation of α₁-receptors labelled by prazosin (K(d) 6.5 nM), but showed 100-fold lower affinity and complex binding characteristics to the other two classes of α-adrenergic receptor sites labelled by WB-4101 and yohimbine, respectively. The results show that pirbuterol and timolol are highly β-receptor selective and that hypotensive responses to these drugs are not mediated by the other classes of α-adrenergic receptor determined in this study. However, the hypotensive response to nylidrin may be related to its prazosin-like (α₁-receptor) antagonist properties with additional activity at β-receptors.