Ocular hypotensive effects of lofexidine, an alpha₂‐adrenoreceptor agonist

Abstract

The present study examines the ocular hypotensive efficacy end pupillary response of the alpharadrenergic receptor agonists lofexidine and clonidine. The topical administration of lofexidine to rabbit eyes in concentrations ranging from 0.25 to 5%, produced a dosedependent bilateral reduction in intraocular pressure (IOP), with the contralateral (untreated) eye exhibiting a significantly greater reduction in IOP than the ipsilateral (treated) eye, particularly at the lower concentrations. The maximum decrease in IOP was observed at 60 min postdrug with the IOP recovering gradually to predrug values with time. Pupillary dilatation was observed only in the drug-treated eye. Unlike lofexidine, clonidine had no effect on pupillary diameter. Clonidine decreased IOP predominantly in the untreated contralateral eye at doses ranging from 0.625% to 5%, whereas a significant ocular hypertensive effect of clonidine was noted at the 7.5% dose in the treated ipsilateral eye. The present data provide evidence that topically administered lofexidine lowers IOP in normotensive New Zealand White (NZW) rabbits.

Ocular Hypotensive Effects of Medetomidine and Its Analogs

“…This phenomenon has been reported for other 0C2-agonists, e.g. lofexidine (6), UK-14,304-18 (1) and moxonidine (4). It was proposed that the delayed ipsilateral IOP response was possibly due to competing activities at peripheral postjunctional (contraction of the extraocular muscle) and prejunctional (sympathetic nerve ending) sites (1).…”

“…Similar properties for clonidine have been reported in the rabbit ciliary process (10). In our previous work with other cc2-agonists, it has been shown that the ranked order of intrinsic activity at inhibiting isoproterenol-stimulated adenylate cyclase was lofexidine = p-amino-clonidine > clonidine (11) and clonidine had a lower intrinsic activity at lowering IOP than lofexidine in normotensive rabbits (6). Similarly, it was found that detomidine had a lesser maximum effect than medetomidine both in lowering IOP and inhibiting adenylate cyclase activity in this experiment.…”

“…This is comparable to that observed by Heath et al (14). This bilateral ocular hypotensive effect following topical unilateral application of drugs has been reported with other ct2-agonists (1,(4)(5)(6). The mechanisms for this contralateral ocular response remain unclear.…”

“…Selective a2-adrenergic agonists decrease the intraocular pressure (IOP) in ocular normotensive animals when applied to cats (1), monkeys (2,3) and rabbits (4)(5)(6). In humans, several 0C2-agonists have been shown to reduce IOP in glaucoma patients (7) and the a2-agonist, apraclonidine (p-amino-clonidine), has recently been approved for the treatment of acute elevation of IOP following laser surgery.…”

Inhibition of Adenylate Cyclase in Bovine Ciliary Process and Rabbit Iris Ciliary Body to Alpha2-Adrenergic Agonists

“…The a2-adrenergic agonists (B-HT920, B-HT 933, UK-14,308-18, clonidine, lofexidine) have been reported to lower intraocular pressure (IOP) in experimental animals and in humans (1)(2)(3)(4)(5). Innemee et al, (1) demonstrated that cc2-adrenoceptor agonists are generally more effective ocular hypotensive agents than ai-agonists in laboratory animals.…”