5-Hydroxtryptamine1D receptor agonism predicts antimigraine efficacy.
The interactions of four abortive anti-migraine agents and four prophylactic anti-migraine agents with 5-HT1D receptors in bovine brain were analyzed using radioligand binding techniques and adenylate cyclase assays. In bovine caudate, the affinities of abortive anti-migraine agents (i.e. 5-hydroxytryptamine, ergotamine, dihydroergotamine, sumatriptan) for 5-HT1D receptors range from 4.0-34 nM while the affinities of prophylactic anti-migraine agents (i.e. methysergide, amitriptyline, (-)propranolol, verapamil) range from 46-11,000 nM. In adenylate cyclase studies in bovine substantia nigra, all four abortive anti-migraine agents dose-dependently inhibit forskolin-stimulated adenylate cyclase activity, a biochemical effect mediated by 5-HT1D receptors. No agonist effect on cyclase activity is observed with the four prophylactic anti-migraine agents. These data support the hypothesis that abortive anti-migraine agents are 5-HT1D receptor agonists and that this effect may underlie their anti-migraine efficacy.
Deliganis
A V
AV
Department of Neurology, Stanford University Medical Center, CA 94305-5235.
Peroutka
S J
SJ
D000067956:Adenylyl Cyclase Inhibitors; D000639:Amitriptyline / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002421:Caudate Nucleus / Q000378:metabolism; D004087:Dihydroergotamine / Q000378:metabolism / Q000494:pharmacology; D004878:Ergotamine / Q000378:metabolism / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008784:Methysergide / Q000378:metabolism / Q000494:pharmacology; D008881:Migraine Disorders / Q000188:drug therapy / Q000378:metabolism*; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology; D018170:Sumatriptan; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D007211:Indoles; D011985:Receptors, Serotonin; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D000639:Amitriptyline; D012701:Serotonin; D004087:Dihydroergotamine; D018170:Sumatriptan; D014700:Verapamil; D004878:Ergotamine; D008784:Methysergide