GAT564 (Compound 15d) is a potent allosteric modulator of cannabinoid 1 receptor ( CB1R ) with EC 50 s of 87 and 320 nM respectively for cAMP and β-arrestin2. GAT564 markedly promotes orthosteric ligand binding to hCB1R. GAT564 is efficacious as a topical agent that significantly reduces intraocular pressure (IOP) in the ocular normotensive murine model of glaucoma.