Abstract
The antagonist effects of indoramin were investigated in rabbit perfused ear artery, common carotid artery, and human perfused temporal artery preparations. Indoramin was a potent competitive antagonist of the constrictor effects of noradrenaline (NA) in all three preparations, pA2 values being 7.77 for the ear artery, 8.20 for the common carotid artery and 7.46 for the human temporal artery. The constrictor actions of serotonin (5-hydroxytryptamine, 5-HT) were competitively antagonized by indoramin. The pA2 values obtained in the rabbit common carotid and human temporal artery (5.92 and 6.25, respectively), were lower than those for NA in the same preparations and lower than that obtained in the rabbit perfused ear artery (7.55). Indoramin was a potent competitive antagonist (pA2:8.31) of histamine-induced vasoconstriction in the rabbit perfused ear artery preparation. These results can be explained on the basis of previous findings that the action of 5-HT in the rabbit ear artery is mediated via an alpha-adrenoceptor, and that the rabbit common carotid artery contains true 5-HT receptors. The findings suggest that specific 5-HT receptors may be present in the human temporal artery and that alpha-adrenoceptor antagonism may be the pharmacological property of most relevance to the efficacy of indoramin in migraine prophylaxis.
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