5-HT1F RECEPTOR AGONISTS INHIBIT NEUROGENIC DURAL INFLAMMATION IN GUINEA-PIGS

THE serotonin (5-HT) receptor subtype mediating inhibition of neurogen ic dural inflammation in guinea pigs was investigated using a series o f serotonin agonists differing affinities for the 5-HT1B, 5-HT1D and 5 -HT1F receptors. When agonist potencies for inhibiting neurogenic infl ammation were compared with affinities for these receptor subtypes, a significant positive correlation was seen only with the 5-HT1F recepto r. The potency of agonists in inhibiting adenylate cyclase in cells tr ansfected with human 5-HT1F receptor was also highly correlated with t heir potency in the animal model of migraine. In situ hybridization de monstrated 5-HT1F receptor mRNA in guinea pig trigeminal ganglion neur ons. These data suggest that the 5-HT1F receptor is a rational target for migraine therapeutics.