SB-271046 is a potent, selective and orally active antagonist of 5-HT6 receptor (pKi = 8.9 in HeLa cell in vitro)
5-HT receptor is a G-protein coupled receptor for 5-hydroxytryptamine (serotonin) that found in nerve systems. It also functions as receptor for various alkaloids and psychoactive substances.
In native brain tissue, SB-271046 exhibits high affinity for human recombinant 5-HT6 receptors and 5-HT6 receptors. SB-271046 has a 200 fold greater selectivity over all other 5-HT receptors subtypes tested. [1]
In rat MEST (maximal electroshock seizure threshold) test, SB-271046 increases the seizure threshold over a wide range of dose with a minimum effective dose of 40.1 mg kg71 p.o. and maximum effect at 4 h post-dose. [1] In rat Morris water maze that measuring behavior acquisition and retention, galanthamine and SB-271046 combined treatment reverses the scopolamine- or MK-801-induced learning impairments. [2]
References:
1. Routledge C, Bromidge SM, Moss SF et al. Characterization of SB-271046: a potent, selective and orally active 5-HT (6) receptor antagonist. Br J Pharmacol. 2000 Aug; 130(7):1606-12.
2. Marcos B, Chuang TT, Gil-Bea FJ, Ramirez MJ. Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat. Br J Pharmacol. 2008 Oct;155(3):434-40.