LY-2624803


LY-2624803, also known as HY-10275, is a dual histamine H1 receptor and serotonin 5-HT2A receptor antagonist which was under development for the treatment of insomnia but was never marketed. It is taken orally.

Pharmacology

The drug is described as a high-affinity highly selective histamine H1 receptor inverse agonist with additional strong serotonin 5-HT2A receptor antagonism or inverse agonism. The precise balance of these activities has not been disclosed. It was found to dose-dependently increase slow wave sleep in animals. In a phase 2 clinical trial, the drug was found to significantly reduce wake after sleep onset as well as to reduce sleep onset latency in humans. No next-day residual fatigue was observed. In terms of chemical structure, it is an analogue of tricyclic compounds like quetiapine and amoxapine.

Development

LY-2624803 was under development by Eli Lilly and Hypnion. Its development was discontinued in 2011. The drug reached phase 2 trials prior to the discontinuation of its development. Besides doxepin and esmirtazapine, it was one of the only histamine H1 receptor antagonists to have reached phase 2 trials for treatment of insomnia.