Relative importance of central imidazoline receptors for the antihypertensive effects of moxonidine and rilmenidine.
OBJECTIVE
To determine the involvement of central imidazoline receptors in the cardiovascular actions of the antihypertensive agents moxonidine, rilmenidine and clonidine administered systemically.


METHODS
We determined the relative potency of these drugs with respect to their effects on mean arterial pressure and heart rate by performing cumulative intravenous dose-response relationship studies in six conscious rabbits. In another eight rabbits with implanted fourth-ventricular catheters, we investigated the central effects of three cumulative doses of an l1-imidazoline/ alpha 2-adrenoceptor antagonist, efaroxan, and of an alpha 2-adrenoceptor antagonist, 2-methoxyidazoxan (2-Ml), on the hypotension and bradycardia elicited by a single intravenous dose of the above agents. The doses of antagonists were matched for an equal reversal of the hypotension induced by fourth-ventricular alpha-methyldopa (an alpha 2-adrenoceptor agonist) and hence for similar alpha 2-adrenoceptor blockade.


RESULTS
Moxonidine and rilmenidine were sevenfold and eightfold less potent, respectively, than was clonidine in eliciting hypotension. By comparison, moxonidine and clonidine were more potent than was rilmenidine in producing bradycardia. Efaroxan and 2-Ml reversed the hypotension and bradycardia induced by a single dose of all three agents dose-dependently. However, efaroxan was more effective than was 2-Ml at reversing the effects of rilmenidine and moxonidine. Complete reversal of their hypotensive effect was observed with the highest dose of efaroxan but the highest dose of 2-Ml reversed approximately 50% of that effect. In contrast, the two antagonists were equally effective at reversing the responses to clonidine.


CONCLUSIONS
These results suggest that the hypotension and bradycardia induced by intravenous administration of moxonidine and rilmenidine were mediated mainly by actions on central imidazoline receptors whereas clonidine appears to act predominantly on central alpha 2-adrenoceptors.
Chan
C K
CK
Neuropharmacology Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
Head
G A
GA
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006328:Cardiac Catheterization; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007275:Injections, Intravenous; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D011817:Rabbits; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D000077769:Rilmenidine; D013997:Time Factors
D058669:Adrenergic alpha-2 Receptor Antagonists; D000959:Antihypertensive Agents; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D010080:Oxazoles; D011955:Receptors, Drug; C043482:moxonidine; C058525:2-methoxyidazoxan; C062597:efaroxan; D003000:Clonidine; D000077769:Rilmenidine; D019329:Idazoxan