title: 5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs.
abstract: The serotonin (5-HT) receptor subtype mediating inhibition of neurogenic dural inflammation in guinea pigs was investigated using a series of serotonin agonists with differing affinities for the 5-HT1B, 5-HT1D and 5-HT1F receptors. When agonist potencies for inhibiting neurogenic inflammation were compared with affinities for these receptor subtypes, a significant positive correlation was seen only with the 5-HT1F receptor. The potency of agonists in inhibiting adenylate cyclase in cells transfected with human 5-HT1F receptor was also highly correlated with their potency in the animal model of migraine. In situ hybridization demonstrated 5-HT1F receptor mRNA in guinea pig trigeminal ganglion neurons. These data suggest that the 5-HT1F receptor is a rational target for migraine therapeutics.
authors.affiliation: Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Johnson
authors.forename: J M
authors.initials: JM
authors.lastname: Schaus
authors.forename: M M
authors.initials: MM
authors.lastname: Durkin
authors.forename: J E
authors.initials: JE
authors.lastname: Audia
authors.forename: S W
authors.initials: SW
authors.lastname: Kaldor
authors.forename: M E
authors.initials: ME
authors.lastname: Flaugh
authors.forename: N
authors.initials: N
authors.lastname: Adham
authors.forename: J M
authors.initials: JM
authors.lastname: Zgombick
authors.forename: M L
authors.initials: ML
authors.lastname: Cohen
authors.forename: T A
authors.initials: TA
authors.lastname: Branchek
authors.forename: L A
authors.initials: LA
authors.lastname: Phebus
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000187:drug effects*; D014363:Tryptamines; D000096642:Receptor, Serotonin, 5-HT1F
chemical_list: D001549:Benzamides; D002227:Carbazoles; D007211:Indoles; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D000096642:Receptor, Serotonin, 5-HT1F; C108218:4-fluoro-N-(3-(1-methyl-4-piperidinyl)-1H-indol-5-yl)benzamide; C108220:LY 306258; C108219:LY 302148; C106783:naratriptan