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Clonidine has a contractile effect in the isolated rabbit aorta which can be blocked by alpha-adrenergic antagonist, phentolamine. Histamine H1-receptor blocker, mepyramine, partly antagonizes its myotropic effect and histamine H2-blocker, metiamide, potentiates it, implying a histaminergic component in the response. Inhibition of histamine synthesis by histidine decarboxylase inhibitor, GYKI 11.121, reduces clonidine-induced contraction in this preparation, while diamine oxidase inhibition by aminoguanidine potentiates it. This is indirect evidence of the possibility of de novo histamine synthesis by clonidine, which may take part on the contractile effect of the drug in the rabbit aorta.
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