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 (WASO) (by 35minutes at 1mg and by 62minutes at 3mg) 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 (Silenor; SO-101) and esmirtazapine (ORG-50081), it was one of the only histamine H1 receptor antagonists to have reached phase 2 trials for treatment of insomnia.
See also Serotonin 5-HT2A receptor antagonist List of investigational insomnia drugs
References