Table 2.

Summary of H3R antagonists that have been in clinical and preclinical trials in ASD and related brain disorders.

Disorder	H3R antagonist	Clinical phase	Pharmacological effect	Reference
ASD	Ciproxifan	Preclinical	Improving some social impairments and stereotypies in mice.	(Baronio et al., 2015)
	DL77	Preclinical	Palliated sociability deficits and stereotypies.	(Eissa et al., 2018a)
	ABT-239	Preclinical	Improvement in social memory.	(Fox et al., 2005)
	E100	Preclinical	Ameliorated repetitive compulsive behaviors in a mouse model of ASD.	(Eissa et al., 2019)
ADHD	JNJ-31001074	Clinical	No significant improvements in adult patients.	(Weisler et al., 2012; Sadek et al., 2016c)
AD	ABT-288	Clinical	A randomized study did not demonstrate any significant improvements in mild to moderate AD dementia.	(Haig et al., 2014b)
	Ciproxifan	Preclinical	Improvement in increased locomotor activity in transgenic mice. Enhancement in memory deficit.	(Bardgett et al., 2011)
	GSK239512	Clinical	Positive improvement in episodic memory in patients with mild to- moderate AD. No improvement in executive function/working memory for subjects with mild to- moderate AD.	(Nathan et al., 2013; Grove et al., 2014)
	JNJ-10181457	Preclinical	Reversed scopolamine induced-cognitive deficits in rats. Regulated ACh neurotransmission.	(Galici et al., 2009)
Cognitive impairments	ABT-239	Preclinical	Attenuated scopolamine-induced deficits in cognitive tests in rodents. Improvement in social memory.	(Brown et al., 2013)
	A-431404	Preclinical	Ameliorated cognitive impairments induced by ketamine and MK-801.	(Brown et al., 2013)
	DL77	Preclinical	Improvement of cognitive deficits through different memory stages in rats.	(Eissa et al., 2018a)
	GSK189254	Preclinical	Attenuated scopolamine-induced deficits in cognitive tests in rodents.	(Ligneau et al., 2007; Medhurst et al., 2007a; Medhurst et al., 2007b; Galici et al., 2009)
	GSK207040
	GSK334429
	Pitolisant
Epilepsy	DL77	Preclinical	Increased anticonvulsant activity in epilepsy models.	(Sadek et al., 2016c)
Narcolepsy	Pitolisant	Clinical	Reduced excessive daytime sleepiness.	(Baronio et al., 2014)
SCH	ABT-288	Clinical	Failed on providing cognitive improvements to patients.	(Haig et al., 2014a)
	ABT-239	Preclinical	Attenuated cognitive deficits caused by ketamine and MK-801.	(Brown et al., 2013)
	A-431404	Preclinical	Attenuated cognitive deficits caused by ketamine and MK-801.	(Brown et al., 2013)
	Ciproxifan	Preclinical	Enhancement of prepulse inhibition.	(Browman et al., 2004)
	SAR 110894	Preclinical	Normalized impaired social behavior.	(Griebel et al., 2012)
	Thioperamide	Preclinical	Enhancement of prepulse inhibition.	(Browman et al., 2004)
	Pitolisant	Preclinical	Reduced locomotor hyperactivity elicited by methamphetamine or dizolcipine. Abolished the apomorphine-induced deficit in prepulse inhibition.	(Ligneau et al., 2007)