Potential mechanisms of moxonidine-induced ocular hypotension: role of norepinephrine.
In rabbit's aqueous humor, norepinephrine, epinephrine, dopamine and serotonin were detected simultaneously by a high performance liquid chromatography with electrochemical detection. Furthermore, the changes in catecholamine levels in aqueous humor were evaluated after topical application of moxonidine, an imidazoline1/alpha 2 receptor agonist, in the presence and absence of efaroxan. The level of norepinephrine in aqueous humor was reduced by moxonidine treatment. However, under the same set of conditions, there were no significant changes in the levels of dopamine, epinephrine or serotonin. Pretreatment with efaroxan antagonized moxonidine-induced suppression of norepinephrine levels. In other in vivo experiments, moxonidine caused a decrease in intraocular pressure which was antagonized by pretreatment with efaroxan. In the superior cervical ganglion preparation, norepinephrine release was increased 5-fold by the presence of a high K+ medium. The K(+)-evoked norepinephrine secretion was reduced by 55% by moxonidine. Pretreatment with efaroxan blocked the moxonidine-induced inhibition of norepinephrine release. It is concluded that inhibition of norepinephrine release from the superior cervical ganglion and suppression of aqueous norepinephrine levels contribute to the moxonidine-induced lowering of intraocular pressure. Moreover, the antagonism of moxonidine's in vivo and in vitro effects by efaroxan suggests the involvement of imidazoline1 receptors, but does not preclude activity on alpha 2 adrenoceptors.
Chu
T C
TC
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia, USA.
Socci
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RR
Ogidigben
M J
MJ
Potter
D E
DE
D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007429:Intraocular Pressure; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D015814:Ocular Hypotension / Q000139:chemically induced* / Q000378:metabolism; D011817:Rabbits; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000378:metabolism
D000959:Antihypertensive Agents; D001572:Benzofurans; D007093:Imidazoles; C043482:moxonidine; C062597:efaroxan; D004298:Dopamine; D009638:Norepinephrine