Table 1.

α7 nAChR agonists and PAM in clinical trials.

Compound	Classification	Potency & efficacy	Animal model on CNS disorders	Indication	Clinical status (Sponsor)
Tropisetron	Partial agonist	Binding affinity:	Mice: phencyclidine-induced cognitive deficits75.	Pain	Phase IV (completed in 2009)
		Ki: 6.9 nmol/L (in rα7)73
					(University Hospital, Clermont-Ferrand)
		Electrophysiology activity:	Rats: young and aged rats76; naloxone-induced place aversion77.
		Hα7 in oocytes: EC50 = 0.6 μmol/L; Emax = 25%74
				Smoking cessation; schizophrenia	Phase III (completed in 2011)
		Mα7 in oocytes: EC50 = 1.3 μmol/L; Emax = 36%73
					(Baylor College of Medicine)
GTS-21/DMXB-A	Partial agonist	Binding affinity:	Rats: normal or isoflurane-induced cognitive impairment aged rats80., 81., 82.; ibotenic acid-induced dementia83; mecamylamine-caused learning impairment84; auditory gating in isolation-reared rats85; apomorphine/MK-801-elicited PPI deficits86., 87..	Schizophrenia	Phase II (completed in 2015)
		Ki: 2000 nmol/L (in hα7)78
		Electrophysiology activity:
		Hα7 in oocytes: EC50 = 11.0 μmol/L; Emax = 9%79			(University of Colorado)
		Rα7 in oocytes: EC50 = 5.2 μmol/L; Emax = 32%79		AD; ADHD	Phase II (completed in 2008)
					(CoMentis)
			Mice: Aβ-induced cognitive deficits45; deficient sensory inhibition88; aggressive behavior in mouse models89.
				Tobacco use disorder	Phase II (not yet recruiting)
			Rabits: aged rabbits90., 91..
					(University of Florida)
			Monkeys: normal monkeys in DMTS task78; Ketamine-induced cognitive deficit92.
ABT-126	Agonist	Binding affinity:	Monkeys: Parkinsonian monkeys95.	AD	Phase II (terminated in 2014)
		Ki: 12–14 nmol/L (in hα7, rα7 and mα7)93., 94.
					(AbbVie)
				Schizophrenia	Phase II (terminated in 2014)
					(AbbVie)
AZD0328	Partial agonist	Binding affinity:	Mice: NOR in normal mice96., 97..	AD	Phase I (completed in 2008)
		Ki: 3.0 and 4.7 nmol/L (in hα7 and rα7)96
		Electrophysiology activity:	Monkeys: normal monkeys in delayed response task98.
		Hα7 in oocytes: EC50 = 338 nmol/L; Emax = 64.7%96			(AstraZeneca)
				Schizophrenia	Phase II (terminated in 2008)
		Rα7 in oocytes: EC50 = 150 nmol/L; Emax = 61.0%96
					(AstraZeneca)
BMS-933043	Partial agonist	Binding affinity:	Rats: MK-801-induced cognitive deficits73; S(+)ketamine-induced sensory gating deficits73.	Schizophrenia	Phase I (completed in 2013)
		Ki: 8.1 and 3.3 nmol/L (in hα7 and rα7)73
		Ca2+ flux assays:
		Hα7 in HEK293 cell line: EC50 = 23.4 nmol/L73			(Bristol-Myers Squibb)
		Electrophysiology activity:
		Hα7 in oocytes: EC50 = 0.29 μmol/L;Emax = 24%73
		Rα7 in oocytes: EC50 = 0.14 μmol/L; Emax = 27%73
			Mice: MK-801-induced cognitive deficits73.
EVP-6124/ Encenicline	Partial agonist	Binding affinity:	Rats: scopolamine-induced deficit99; delay-dependent forgetting in the NOR100; low attentive rats101.	AD; dementia	Phase III (terminated in 2017)
		Ki: 9.98 nmol/L (in rα7)99
					(FORUM)
		Electrophysiology activity:
		Hα7 in oocytes: EC50 = 0.39 μmol/L; Emax = 42%99		Schizophrenia; impaired cognition	Phase III (completed in 2016)
					(FORUM)
				Nicotine dependence; smoking cessation	Phase II (terminated in 2015)
					(A. Eden Evins)
MEM3454/RG3487	Partial agonist	Binding affinity:	Rats: attentional performance in normal rats103; aged rats102; apomorphine-induced deficits in sensorimotor gating102.	AD	Phase II (completed in 2007)
		Ki: 6 nmol/L (in rα7)102
		Electrophysiology activity:			(Memory)
		Hα7 in oocytes: EC50 = 0.8 μmol/L; Emax = 63%102
				Schizophrenia	Phase II (unknown)
		Hα7 in QM cell line: EC50 = 7.7 μmol/L; Emax = 69%102			(Memory)
AQW051	Partial agonist	Binding affinity:	Rats: aged rats05105	Schizophrenia	Phase II (completed in 2013)
		Ki: 27 nmol/L104
		Ca2+ flux assays:	Mice: NOR in normal mice105
		Hα7: EC50 = 7.4 μmol/L; Emax = 73%105	Monkeys: Parkinsonian monkeys106		(Novartis)
		Electrophysiology activity:
		Hα7 in oocytes: EC50 = 7.5 μmol/L; Emax = 75%105		Levodopa-induced dyskinesia in PD	Phase II (completed in 2013)
					(Novartis)
				AD	Phase II (terminated in 2009)
					(Novartis)
TC-5619	Full agonist	Binding affinity:	Mice: th(tk–)/th(tk–) mice108; apomorphine-induced PPI deficits108; NOR in normal mice108.	Schizophrenia	Phase II (completed in 2013)
		Ki: 1 and 1.4 nmol/L (in hα7 and rα7)107., 108.
		Electrophysiology activity:			(Targacept)
		Hα7 in oocytes: EC50 = 33 nmol/L; Emax = 100%108., 109.		AD	Phase I (completed in 2011)
		Rα7 in GH4C1 cell line: EC50 = 17 nmol/L; Emax = 76%107			(Targacept)
				ADHD	Phase II (completed in 2012)
					(Targacept)
SSR-180711	Partial agonist	Binding affinity:	Rats: MK-801/PCP-induced cognitive deficits111; depressive disorders rates111; neurodevelopmental latent inhibition models of schizophrenia112.	AD	Phase II (terminated in 2008)
		Ki: 14 and 22 nmol/L (in hα7 and rα7)110
					(Sanofi)
		Electrophysiology activity:
		Hα7 in oocytes: EC50 = 4.4 μmol/L; Emax = 51%110	Mice: chronic mild stress model113; Aβ-induced memory deficits114; phencyclidine-induced cognitive deficits115; forced swim and tail suspension tests116
		Hα7 in GH4C1 cell line: EC50 = 0.9 μmol/L; Emax = 36%110
APN1125	Partial agonist	Electrophysiology activity:	Rats: NOR in normal rats117	Schizophrenia	Phase I / Phase II (suspended in 2016)
(Structure Undisclosed)		Hα7 in oocytes: EC50 = 1.16 μmol/L; Emax = 41%117
					(CoMentis)
AVL-3288/XY4083/CCMI	Type I PAM	Electrophysiology activity:	Mice: DBA/2 mouse model of sensory-gating deficit118; MK-801-induced hyperlocomotion mode eight-arm radial maze in normal mice118; NOR in normal mice119.	Schizophrenia; schizoaffective disorder	Phase I (recruiting)
		Hα7 in oocytes: EC50 = 0.7 μmol/L; Emax = 9 folds118			(New York State Psychiatric Institute; University of Colorado)
			Rats: 5-CSRTT in normal rats119; ketamine-induced cognitive deficits and social withdrawal120.

DMTS, delayed matching-to-sample; NOR, novel object recognition; PCP, neonatal phencyclidine; 5-CSRTT, five-choice serial reaction time task.

Indications and clinical status of α7 nAChR modulators above are obtained from https://clinicaltrials.gov/.