GAT229 is a positive allosteric modulator of cannabinoid receptor 1 (CB1) and the S-(-) enantiomer of the CB1 modulator GAT211. It does not activate the receptor on its own but enhances the binding and activity of CB agonists. GAT229 (1 μM) enhances the binding of the CB1 full agonist CP 55,940 to CHO cells expressing human recombinant CB1 (hCB1), as well as the activity of 2-arachidonoyl glycerol , arachidonoyl ethanolamide , and CP 55,940 in arrestin2 recruitment assays and increases ERK1 2 and PLCβ3 phosphorylation in HEK293 cells expressing hCB1. GAT229 (1 μM) enhances depolarization-induced suppression of excitation but does not inhibit excitatory postsynaptic currents (EPSCs) in murine autaptic hippocampal neurons. GAT229 (0.2%, topical) reduces intraocular pressure by 5.8 and 7.7 mm Hg after 6 and 12 hours, respectively, in a transgenic mouse model of ocular hypertension using nose, ear, eye mutation (nee) mice.
AM8936 is a well-balanced and highly potent agonist for the cannabinoid receptor type-1 (CB1) in functional assays, with EC50 values of 8.6 nM and 1.4 nM for the rat CB1 (rCB1) and human CB1 (hCB1) receptors, respectively. It demonstrates a strong affinity for the rat CB1 receptor, exhibiting a K i value of 0.55 nM. In vivo studies have confirmed that AM8936 is a powerful and effective agonist for the CB1 receptor. Due to its therapeutic potential, AM8936 is particularly valuable for research focused on central nervous system disorders, metabolic disorders, pain management, glaucoma, and other related areas [1].