Ocular actions of moxonidine: a possible role for imidazoline receptors.
Moxonidine (MOX, 4-chloro-N-[4,5 dihydro-1H-imidazol-2-yl]-6-methoxy-2- methyl-5-pyridinamine), a relatively selective alpha-2 agonist, was investigated for effects on: 1) aqueous humor dynamics in normal and unilaterally sympathectomized rabbits; 2) noradrenergic functions in cat nictitating membrane (CNM); 3) [3H]norepinephrine overflow in rabbit iris-ciliary bodies (ICBs) and 4) cyclic AMP (cAMP) accumulation in rabbit ICBs and nonpigmented ciliary epithelial (NPE) cells. Unilateral, topical administration of MOX to the normal rabbit eyes produced decreases in intraocular pressure, aqueous humor flow rate and ipsilateral increases in pupil diameter. Ocular hypotensive response to MOX was inhibited by bilateral, topical pretreatment with idazoxan, an alpha-2/imidazoline antagonist, and efaroxan, an imidazoline antagonist. In sympathectically denervated rabbit eyes, MOX did not lower intraocular pressure or decrease aqueous humor flow rate. MOX suppressed, dose dependently, contractions of the CNM elicited by electrically stimulating the preganglionic sympathetic trunk, an effect antagonized by rauwolscine, an alpha-2 antagonist. In other experiments, MOX caused a dose-related inhibition of [3H]norepinephrine release from field-stimulated ICBs, an effect antagonized by efaroxan. MOX antagonized isoproterenol-induced cAMP accumulation in rabbit ICBs and NPE cells, an effect inhibited by rauwolscine. These results demonstrate that MOX: 1) produces ocular hypotension in rabbits by suppressing aqueous humor flow; 2) antagonizes electrically induced contractions of the CNM by inhibiting sympathetic neuronal function; 3) suppresses norepinephrine release of rabbit ICBs, an effect that was inhibited by efaroxan and 4) prevents isoproterenol-induced cAMP accumulation in the rabbit ICBs and NPE cells via action on alpha-2 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Ogidigben
M
M
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia.
Chu
T C
TC
Potter
D E
DE
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects; D002415:Cats; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005123:Eye / Q000187:drug effects*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C043482:moxonidine; D000242:Cyclic AMP