Medetomidine-induced alterations of intraocular pressure and contraction of the nictitating membrane.
The alpha-2 adrenoceptor agonist, medotomidine (MED), was examined for effects on: (1) intraocular pressure (IOP) in normal and sympathectomized (SX) rabbits; (2) IOP in normal rabbits pretreated with the alpha-2 antagonist idazoxan; (3) contractions of the cat nictitating membrane (CNM) elicited by nerve stimulation and intra-arterial (IA) norepinephrine. Unilateral topical administration of MED (7.5-75 micrograms) caused dose-dependent, bilateral IOP reduction in normal eyes, but MED (25 micrograms) had no appreciable hypotensive activity in SX eyes. The ocular hypotensive effect of MED (25 micrograms) was antagonized by treatment with idazoxan (100 micrograms, bilaterally), a relatively selective alpha-2 antagonist. MED and dexmedetomidine (DMED) also inhibited frequency-related contractions of CNM induced by electrical stimulation of the cervical sympathetic trunk. Rauwolscine (100 micrograms, IA) shifted the MED dose response in the CNM to the right indicative competitive antagonism, whereas SK&F 104078 (300 micrograms, IA), a relatively dose-selective postjunctional alpha-2 antagonist, had no effect on DMED suppression. These results show that MED lowers IOP in part, by interacting with alpha-2 adrenoceptors located on sympathetic nerve endings. An effect of MED on imidazoline sites may also be possible.
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495.
D E
DE
Potter
M J
MJ
Ogidigben
D000287:Administration, Topical; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D019329:Idazoxan; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D020926:Medetomidine; D009119:Muscle Contraction; D009541:Nictitating Membrane / Q000187:drug effects* / Q000294:innervation; D011817:Rabbits; D013562:Sympathectomy
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D020926:Medetomidine; D019329:Idazoxan