5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs.
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.
Johnson
K W
KW
Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, USA.
Schaus
J M
JM
Durkin
M M
MM
Audia
J E
JE
Kaldor
S W
SW
Flaugh
M E
ME
Adham
N
N
Zgombick
J M
JM
Cohen
M L
ML
Branchek
T A
TA
Phebus
L A
LA
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
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