Sb-742457

SB-742457 is an orally bioavailable antagonist of the serotonin (5-HT) receptor subtype 5-HT₆ (K_i = 1.4 nM). SB-742457 (1 μM) also binds to 5-HT_1B, 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors with high affinity. SB-742457 reduces 5-HT₆ activation of G_s-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.

SB 742457 is a selective 5-HT6 receptor antagonist which is known to be involved in improving cognitive function.

5-HT6

[1] aaron t. t. chuang, andrew foley, perdita l. pugh, david sunter, xin tong, ciaran regan, lee a. dawson, andrew d. medhurst, neil upton.5-ht6 receptor antagonist sb-742457 as a novel cognitive enhancing agent for alzheimer’s disease. alzheimer's & dementia: the journal of the alzheimer's association volume 2, issue 3, supplement, pages s631–s632, july 2006