Dual effect of dihydroergotamine at vascular 5-hydroxytryptamine receptors in pithed rats

Dihydroergotamine (DHE), administered intravenously to pithed normotensive rats, increased the mean arterial blood pressure dose-dependently. This pressor effect was noncompetitively inhibited by the 5-hydroxytryptamine (5-HT) receptor antagonists pizotifen and cyproheptadine (0.1 mg/kg each). The alpha 1-adrenoceptor blocker prazosin (1 mg/kg) had no influence on the DHE effect whereas the alpha 2-adrenoceptor blocker yohimbine, at the same dose, proved to be a noncompetitive inhibitor of this pressor effect. The results indicate that both the 5-HT receptors and alpha 2-adrenoceptors are involved in the DHE-induced vasoconstriction. On the other hand, in pithed normotensive rats, DHE proved to be a potent inhibitor of the pressor response to 5-HT but it did not inhibit that to noradrenaline. The results obtained characterize DHE as a noncompetitive dualist at vascular 5-HT receptors.