Pharmacodynamics and pharmacokinetics of dihydroergotamine (DHE) in conscious beagle dogs

Dihydroergotamine (DHE) elicits selective and longlasting venoconstrictor activity though the drug disappears rapidly from the blood. Changes in the diameter of the saphenous vein were determined in conscious beagle dogs and compared to plasma level-time curves of DHE and its metabolites. After both intravenous and oral administration of DHE the venoconstrictor response is of markedly longer duration than would be expected on the basis of the half life for elimination of DHE from blood. Furthermore, 3 out of 5 of the main metabolites of DHE elicited considerable constrictor effects when infused locally into the vein. It is suggested that the long duration of the DHE-induced venoconstriction is due to an extremely slow dissociation of the drug from its receptor sites on the venous smooth muscle cell and to the formation of active metabolites.