Dual Effect of Dihydroergotamine at Vascular 5-Hydroxytryptamine Receptors in Pithed Rats

Abstract

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 α₁-adrenoceptor blocker prazosin (1 mg/kg) had no influence on the DHE effect whereas the α₂-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 α₂-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.

Endothelial 5‐HT receptors mediate relaxation of porcine pulmonary arteries in response to ergotamine and dihydroergotamine

“…The vasoconstrictor effect of DHE is due, in part, to activation of 5-hydroxytryptamine (5-HT) receptors (Muller-Schweinitzer, 1984;Glusa & Markwardt, 1984;Muller et al, 1988). Moreover, venoconstrictor responses to dihydroergocristine and DHE of canine saphenous veins are mediated through 5-HTI-like receptors (MullerSchweinitzer, 1990).…”