Ocular Hypotensive Effects of Medetomidine and Its Analogs

Abstract

The ocular hypotensive effects of medetomidine, a relatively selective (X2-agonist, and its analogs were tested in rabbits and cats and their inhibition of adenylate cyclase in the isolated bovine ciliary process was also studied. It was found that topical unilateral administration of medetomidine (0.5-2.0%) to the normotensive rabbits produced a dose-dependent bilateral decrease in IOP with peak reduction in IOP at 2 hr in the treated eye and 1 hr in the untreated eye. A dose-dependent mydriasis was also observed in the treated eye. The dose-response curves of medetomidine and its analogs showed that the ranked order of intrinsic activity at lowering IOP was medetomidine > MPV-1440 > detomidine > MPV-1441 and MPV-305 Bu. At concentrations lower than those used in rabbits, topical application of medetomidine to the normotensive cats lowered IOP in both treated and untreated eyes. Medetomidine and detomidine caused a dose-dependent inhibition of isoproterenol-stimulated adenylate cyclase activity. Detomidine was found to be a partial agonist producing about 43% of maximum inhibition obtained by medetomidine. The IOP efficacy of these <X2-agonists paralleled their effects on adenylate cyclase activity. The results demonstrated that these imidazoline derivatives are effective ocular hypotensive agents which may be useful in understanding the contribution of 0C2-receptors to the regulation of IOP.

The effect of intravenous medetomidine on pupil size and intraocular pressure in normotensive dogs

“…Peripheral a-2 receptors in the eye, both prejunctionally on ocular sympathetic nerve fibres and postjunctionally, are potentially involved in the physiological regulation of IOP. This regulation is achieved by decreasing the stimulated production of cyclic AMP in the ciliary process (4,5). To our knowledge, the effect of medetomidine on the IOP and pupil diameter of the canine eye has not been described previously.…”

“…MedeDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary tomidine is commonly used to sedate animals for non-surgical interventions, such as oral inspection or radiography or as a premedication before general anaesthesia. Studies of normotensive rabbits and cats have demonstrated that medetomidine lowers the IOP after its topical application to the eye (4,5). Peripheral a-2 receptors in the eye, both prejunctionally on ocular sympathetic nerve fibres and postjunctionally, are potentially involved in the physiological regulation of IOP.…”

Naphazoline-induced Suppression of Aqueous Humor Pressure and Flow: Involvement of Central and Peripheral α2/I1Receptors

“…5, 9 and 10 mmHg) with no initial transient hypertension, an effect previously observed following topical ipsilateral applications of certain a 2 / imidazoline agonists (I 1 ) to eyes of light-adapted rabbits (Burke and Potter, 1986;Jin et al, 1991;Potter and Ogidigben, 1991;Ogidigben et al, 1994). The lack of an initial hypertensive response to naphazoline could be due to the fact that the intraocular pressure and sympathetic tone of dark-adapted rabbits are elevated compared to light-adapted rabbits (McLaren, Brubaker and FitzSimon, 1996).…”

Toxic Effects of Mitomycin-C on Cultured Ciliary Process Cells and Trabecular Meshwork Cells

“…Many drugs activate the adenyl cyclase in the ciliary process leading to an accelerated rate of production of intracellular cAMP and aqueous humor formation (33). In glaucoma treatment, many b-blockers also exert their ocular hypotensive action through inhibition of cAMP production in ciliary epithelium and aqueous humor formation (18,34).…”