Table 4.

A short list of preclinical and clinical trials with cytoprotective Sig-1R agonists.

Disease/Drug Candidate		Drug Activities	Preclinical Studies	Refs.	Clinical Trials (Phase 1,2,3)	Refs.
AD	Afobazole	Sig-1R agonist, melatonin (MT₃) agonist	Neuron culture Mice, icv Aβ 25-35 (AD model)	[59, 121, 122]	-	-
	AF710B	Sig-1R agonist, M1 agonist	AD mouse model	[123]	-	-
	Anavex 2-73	Sig-1R agonist, M1 agonist	Mice, icv Aβ 25-35	[124]	-	-
	Anavex 2-73	-	-	-	Phase 1 (max. dose 55mg) Phase 2a (oral, iv adm)	www.anavex.com
	Anavex 2-73+ Donepezil	ChE-ase inhibitor	Mice, icv Aβ 25-35 (AD model)	[126]	-	-
	Anavex Plus (combination of Anavex 2-73 plus Donepezil)	-	Synergistic effect in AD disease models	www.anavex.com	A patent application was filed in 2016 for the combination	www.anavex.com
PD	PRE 084	Sig-1R agonist	PD mouse model (6-OH DOPA lesion)	[116]	-	-
ALS	Cutamesine (SA 4503)	Sig-1R agonist	ALS mouse model SOD1 (G93A) model +NSC34motoneuron cells SOD1 (G93A) mouse	[139] [140] [140] [102]	-	-
ALS	PRE-084	Sig-1R agonist	wobbler mouse	[115]	-	-
HD	PRE-084	Sig-1R agonist	PC63 cells	[141, 142]	-	-
HD	Pridopidine	Sig-1R agonist, DA stabilizer	HD mouse model	[144, 145]	-	-
TBI traumatic brain injury	PPBP	Sig-1R agonist	TBI neonatal mouse model	[154, 155]	-	-
Retinal ganglion cell death	(+) Pentazocine	Sig-1R agonist	Murine retinal cells RGC-5 cells	[157, 158]	-	-
Ischemic stroke	Cutamesine (SA4503)	Sig-1R agonist	-	-	Phase-2 trial	[156]