clemizole analogue 4

Clemizole analogue 4 is a small molecule serotonin receptor agonist developed as a derivative of the antihistamine clemizole. It was designed and synthesized by researchers at the University of California, San Francisco (UCSF) and Oxygen Healthcare Research to investigate the role of serotonin receptors in treating Dravet syndrome, a severe form of childhood epilepsy. The compound exhibits high selectivity for the 5-HT2B receptor (Ki = 612 nM) with minimal binding to 5-HT2A or 5-HT2C receptors. In preclinical studies using scn1lab mutant zebrafish, clemizole analogue 4 demonstrated significant antiepileptic activity by suppressing both convulsive behaviors and electrographic seizure events, suggesting that 5-HT2B receptor activation is a critical mediator of seizure control in this condition.