The objective of this study was to examine the ocular hydrodynamic effects of topically and centrally administered
naphazoline, alone and following pretreatment with
pertussis toxin (PTX) and alpha(2)/I(1)receptor antagonists. Topically and intracisternally administered
naphazoline was examined for 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 unilateral application of
naphazoline (7.5, 25 and 75 micro g; 25 micro l) elicited an ipsilateral dose-dependent
mydriasis (2, 4 and 5.5 mm) that peaked at 2 hr with a duration of up to 5 hr. The IOP decreases induced by
naphazoline were bilateral 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 micro g) elicited significantly greater antagonism of the ocular hypotensive response to
naphazoline than did
rauwolscine (250 micro g) suggesting an involvement of
imidazoline (I(1)) receptors. Intracisternal application of
naphazoline (3.3 micro g) also 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 micro g kg(-1), i.a.) rabbits, the ocular hypotensive effects of
naphazoline by both routes (topically and centrally) were attenuated by 50--65%. In addition to producing
ocular hypotension, topical application of
naphazoline (75 micro g; 25 micro l) caused significant reduction, from 2.8 to 1.5 micro l min(-1), in aqueous humor flow. These in vivo data indicate that, regardless of route of administration, alteration of aqueous humor flow by
naphazoline was induced by the activation of alpha(2)and I(1)receptors. The ocular hypotensive effects produced by central administration did not result in sedation, therefore, there is the suggestion that central
alpha(2)adrenergic receptors were stimulated minimally by
naphazoline. Thus, these data suggest that ocular hypotensive effects and suppression of aqueous humor flow rate by
naphazoline 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.