GlyT2 Inhibitor

N-Arachidonylglycine (NA-Gly), a carboxylic analog of the endocannabinoid anandamide (AEA), is a GPR18 agonist (EC₅₀ = 44.5 nM). Unlike AEA, N-Arachidonylglycine has no activity at either CB1 or CB2 receptors. N-Arachidonylglycine inhibits GLYT2 (IC₅₀ = 5.1 μM). N-Arachidonylglycine also is an effective activator of endometrial cell migration.

Stearoyl-L-carnitine chloride is an endogenous long-chain acylcarnitine. Stearoyl-L-carnitine chloride is a less potent inhibitor of GlyT2. Stearoyl-L-carnitine chloride inhibits glycine responses by 16.8% at concentrations up 3 μM.

Stearoyl-L-carnitine-d₃ (chloride) is the deuterium labeled Stearoyl-L-carnitine chloride. Stearoyl-L-carnitine chloride is an endogenous long-chain acylcarnitine. Stearoyl-L-carnitine chloride is a less potent inhibitor of GlyT2. Stearoyl-L-carnitine chloride inhibits glycine responses by 16.8% at concentrations up 3 μM.

ALX-1393, a selective GlyT2 inhibitor, has an antinociceptive effect on thermal, mechanical, and chemical stimulations in a rat acute pain model.

RPI-GLYT2-82 is a reversible, blood-brain barrier-permeable allosteric inhibitor of GlyT2 with an IC₅₀ value of 554 nM. RPI-GLYT2-82 also exhibits inhibitory activity against 5-HT2AR and SERT, with IC₅₀ values of 1.9 μM and 4.7 μM, respectively. RPI-GLYT2-82 inhibits pain signals and alleviates allodynia, shows no target-related side effects at the maximum analgesic dose, and has no addictive potential. RPI-GLYT2-82 can be used for the research of neuropathic pain.

GLyT2-IN-3 is a potent GlyT2 inhibitor with a K_D of 23.7 nM. GLyT2-IN-3 inhibits GlyT2-mediated glycine uptake with an IC₅₀ of 19.4 nM. GLyT2-IN-3 shows broad-spectrum antinociceptive effects in three pain models, does not induce sedative effects or motor coordination impairment in mice, and exhibits favorable pharmacokinetic properties in rats with an oral bioavailability of 88.57%, GLyT2-IN-3 can be used for the study of neuropathic pain.