clemizole analogue 6

Clemizole analogue 6 is a small molecule serotonin receptor modulator synthesized as a derivative of the antihistamine clemizole. It was developed to investigate the mechanism of seizure suppression in Dravet syndrome, a severe childhood epilepsy. Research using *scn1lab* mutant zebrafish models demonstrated that clemizole analogue 6 exerts potent antiepileptic activity by selectively binding to and activating the 5-HT2B receptor (5-HT2BR). Unlike its parent compound, analogue 6 shows high selectivity for the 5-HT2B subtype over 5-HT2A and 5-HT2C receptors, with a binding affinity (Ki) of 285 nM for the human 5-HT2BR. It was synthesized through collaborative efforts involving the UCSF Small Molecule Discovery Center and Oxygen Healthcare Research.