TABLE 2

Summary of key preclinical and clinical data on histamine H₃ antagonists that have been reported to advance to the clinical area

	Rat H₃	Human
	Rat H₃	H₃	t_1/2	Clinical Observations and Status
	nM		h
BF2.649 (pitolisant)	17	2.7	10	Efficacy reported in narcoleptic patients and Parkinson's disease.
				Sleep disturbances, insomnia reported in humans.
				Phase 2 trial in schizophrenia ongoing, and phase 3 trial in Parkinson's planned.
PF-03654746	37	3.2	9–18	Sleep disturbances, insomnia in phase 1.
				No efficacy in adult ADHD patients.
				Phase 2 trials in AD and narcolepsy ongoing.
GSK189254	1	0.2	>24	Sleep disturbances, insomnia in humans.
				Discontinued from development in AD.
GSK239512	N.A.	N.A.	N.A.	Advanced to phase 1. Phase 2 trials in AD and schizophrenia ongoing
MK-0249	N.A.	N.A.	N.A.	Sleep disturbances, insomnia in phase 1.
				Alerting effects noted at 67% receptor occupancy.
				No efficacy in schizophrenic patients.
MK-3134	N.A.	N.A.	N.A.	Advanced to phase 1.
ABT-288	8	1.9	N.A.	Phase 2 trials in AD and schizophrenia ongoing.
JNJ-17216498	N.A.	N.A.	N.A.	Advanced to phase 1. Evaluated in patients with narcolepsy and ADHD.