Table 1.

GlyR modulators

Modulator	Group	Potency, μM (EC50)	GlyR selectivity	Techniques employed	Additional targets	Pain models	References
Cannabidiol (CBD), dehydroxyl-cannabidiol (DH-CBD)	Cannabinoid ligand	≈3–5	α1 ≈ α3 > α2	Electrophysiology	GPR55, CB2, TRPV1, PLA2, 5-HT1A	CFA; spinal nerve ligation	[50, 169, 170]
2,6-Di-tert-butylphenol (2,6-DTBP)	Propofol analog	≈20–25	α3 > α1	Electrophysiology	HCN1	Zymosan A, CFA; chronic constriction injury	[29, 137]
	Propofol analog	≈0.001	α1 > α3 = α2	Electrophysiology	ND	Partial nerve ligation, streptozocin-induced diabetic neuropathy	[52]
Gelsemine	Natural alkaloid	≈0.6–49a	α2 ≈ α3 (inhibition) α1 (biphasic modulation)	Electrophysiology,3H-strychnine binding	ND	Formalin-induced pain, bone cancer, spinal nerve ligation	[156, 157]
AM-1488/AM-3607	Tricyclic sulfonamide	≈0.016–0.066	α1 ≈ α2 ≈ α3	Fluorescence-based membrane potential assays	ND	Spared nerve injury	[53, 163]
Compound 19 and (ent2)-20	Azetidine sulfonamides aminothiazole sulfone	0.7 (at α3/β) 2.2 (at α3/β)	α1 = α3  ND	Fluorescence-based chloride flux measurement	ND	ND	[164, 171]
Compound 2 (4-fluoro-N-(2-(quinolin-8-yloxy)ethyl) benzenesulfonamide)	Sulfonamide	≈3.9–8.0	α1 = α3	Fluorescence-based membrane potential assays, electrophysiology (ion flux HT assay and manual patch-clamp)	ND	ND	[162]
Compounds 3 and 6	sesterterpene glycinyl-lactams	≈8.5 (compound 3)	Compound 3: α1 > α3 Compound 6: α3 > α1	Electrophysiology	ND	ND	[159–161]
Tropisetron (ICS-205,930)	tropeines	nM >10 µM fmolar µmolar	α1/β, α2/β potentiation inhibition α1 potentiation α2 inhibition	Electrophysiology Electrophysiology	5-HT3 5-HT3	ND ND	[144] [146]

ND not determined, CFA complete Freund’s adjuvant

^aBiphasic modulation