Discovery of the First Potent, Selective 5-Hydroxytryptamine1D Receptor Antagonist

A series of 5-(piperidinylethyloxy)quinoline 5-hydroxytryptamine1D (5-HT1D) receptor antagonists have been discovered from elaboration of the series of dual 5-hydroxytryptamine1−selective serotonin reuptake inhibitors (5HT1−SSRIs) reported previously. This is the first report of highly potent, selective antagonists for the 5-HT1D receptor, which represents an extremely useful set of pharmacological tools for further understanding the roles of the 5-HT1 receptor subtypes.