<i>N</i>-[3-(2-Dimethylaminoethyl)-2-methyl-1<i>H</i>- indol-5-yl]-4-fluorobenzamide:  A Potent, Selective, and Orally Active 5-HT_1F Receptor Agonist Potentially Useful for Migraine Therapy

Abstract

Recent studies have demonstrated that selective 5-HT(1F) receptor agonists inhibit neurogenic dural inflammation, a model of migraine headache, indicating that these compounds may be effective therapies for the treatment of migraine pain. This communication describes the synthesis and discovery of a novel compound, N-[3-(2-(dimethylamino)ethyl)-2-methyl-1H-indol-5-yl]-4-fluorobenzamide (4), which possesses high binding affinity and selectivity at the 5-HT(1F) receptor relative to more than 40 other serotonergic and nonserotonergic receptors examined.