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 less than 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.
McCarthy
B G
BG
Peroutka
S J
SJ
D000818:Animals; D002417:Cattle; D004087:Dihydroergotamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D018170:Sumatriptan; D013552:Swine
D007211:Indoles; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D013449:Sulfonamides; D004087:Dihydroergotamine; D018170:Sumatriptan