5HT1Freceptor 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-HT1Dand 5-HT1Freceptors. 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-HT1Freceptor. The potency of agonists in inhibiting adenylate cyclase in cells transfected with human 5-HT1Freceptor was also highly correlated with their potency in the animal model of migraine. In situhybridization demonstrated 5-HT1Freceptor mRNA in guinea pig trigeminal ganglion neurons. These data suggest that the 5-HT1Freceptor is a rational target for migraine therapeutics.