Comparative Neuropharmacology of Dihydroergotamine and Sumatriptan (GR 43175)




The potency of dihydroergotamine (DHE) was determined at 13 neurotransmitter receptors using radioligand binding techniques. DHE is a potent agent (i.e. affinity value < 100 nM) at 5-hydroxytryptamine1A (5-HT1A), 5-HT1c, 5-HT1D, 5-HT2, dopamine2, alpha1- and alpha2-adrenergic binding sites. DHE displays moderate affinity (i.e. affinity values = 100 - 1000 nM) for beta-adrenergic and dopamine1 sites and is completely inactive at 5-HT3, muscarinic and benzodiazepine receptors. These results were then compared to similar data on sumatriptan (formerly called GR 43175), a novel acute anti-migraine agent. The only pharmacological property shared by both agents is high affinity for 5-HT1D and 5-HT1A receptors. Therefore, these data suggest that 5-HT1D and/or 5-HT1A receptors may play an important role in the pathophysiology of migraine.