Naphazoline-induced suppression of aqueous humor pressure and flow: Involvement of central and peripheral alpha(2)/I-1 receptors

The objective of this study was to examine the ocular hydrodynamic effects of topically and centrally administered naphazoline, alone and following pr etreatment with pertussis toxin (PTX) and alpha (2)/I-1, receptor antagonis ts. Topically and intracisternally administered naphazoline was examined fo r its ability to alter intraocular pressure (IOP) of rabbits in the absence and presence of receptor antagonists (rauwolscine, efaroxan) and a G(i/o), ribosylating agent PTX. In addition, the topical effects of naphazoline on pupil diameter and aqueous humor flow rate were evaluated. Topical unilate ral application of naphazoline (7.5, 25 and 75 mug: 25 mul) elicited an ips ilateral dose-dependent mydriasis (2, 4 and 5.5 mm) that peaked at 2 hr wit h a duration of up to 5 hr, The IOP decreases induced by naphazoline were b ilateral and dose-dependent (3, 6 and 10 mmHg): the response peaked at 1 hr and lasted for up to 5 hr. Pretreatment with efaroxan (250 mug) elicited s ignificantly greater antagonism of the ocular hypotensive response to napha zoline than did rauwolscine (250 mug) suggesting an involvement of imidazol ine(I-1) receptors. Intracisternal application of naphazoline (3.3 mug) als o produced bilateral reductions (6 mmHg) of IOP that were immediate (10 min post drug) and lasted for approximately 2 hr. In PTX-pretreated (2.5 mug k g(-1). i.a.) rabbits. the ocular hypotensive effects of naphazoline by both routes (topically and centrally) were attenuated by 50-65 %. In addition t o producing ocular hypotension, topical application of naphazoline (75 mug: 25 mul) caused significant reduction, from 2.8 to 1.5 mul min(-1), in aque ous humor flow. These in vivo data indicate that, regardless of route of ad ministration, alteration of aqueous humor flow by naphazoline was induced b y the activation of alpha (2) and I-1 receptors. The ocular hypotensive eff ects produced by central administration did not result in sedation, therefo re, there is the suggestion that central alpha (2) adrenergic receptors wer e stimulated minimally by naphazoline. Thus, these data suggest that ocular hypotensive effects and suppression of aqueous humor flow rate by naphazol ine are mediated, in part, by alpha (2) and/or central I-1 at both central (brain) and peripheral (eye) sites. Moreover, these data indicate that the receptors are linked to PTX-sensitive G((i/o)) proteins. (C) 2001 Academic Press.