SB-742457 is an orally bioavailable antagonist of the serotonin (5-HT) receptor subtype 5-HT6 (Ki = 1.4 nM). SB-742457 (1 μM) also binds to 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C receptors with high affinity. SB-742457 reduces 5-HT6 activation of Gs-mediated cAMP production in a concentration-dependent manner with an EC50 value of 21 nM in NG108-15 neuroblastoma cells. In vivo, SB-742457 (1.5 mg/kg, p.o.) reverses deficits in novel object recognition induced by scopolamine in rats. It also reverses age-induced impairments in spatial memory acquisition and retention in rats in the Morris water maze. SB-742457 (3.0 mg/kg, i.p.) reduces the number of licking bouts by 24% compared with control in rats trained to lick a glucose solution, indicating a role in satiety and obesity management.
