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

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Ogidigben MJ, Chu TC, Potter DE

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

Exp Eye Res. 2001 Mar;72(3):331-9.

PubMed ID

11180982 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Naphazoline	Alpha-1A adrenergic receptor	Protein	Humans	Yes	Agonist	Details
Naphazoline	Alpha-2A adrenergic receptor	Protein	Humans	Yes	Agonist	Details