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In anesthetized rabbits, intracerebroventricular (ICV) administration of the alpha-adrenoceptor agonist, guanfacine, like clonidine, elicited dose-related falls in arterial blood pressure and heart rate. ICV pretreatment with the histamine H2-receptor antagonist, metiamide, significantly reduced the hypotensive and bradycardic responses caused by ICV injection of either guanfacine or clonidine. The present results seem to indicate that the antagonistic effect of metiamide against either guanfacine or clonidine is probably due to its alpha-adrenoceptor blocking action rather than its histamine H2-receptor blocking action, suggesting that these interactions might be of central origin.

Antagonism of hypotensive and bradycardic effects of centrally administered guanfacine by metiamide in anesthetized rabbits.