O1918

O1918 is a selective non-CB₁ receptor and GPR18 antagonist. IC50 & Target: non-CB₁ vascular cannabinoid receptor^[1], GPR18^[2]. In Vivo: Decreases in HR, blood pressure, MBF and RBF by about 20 beats/min, 5-10 mmHg and 0.7 and 0.2 mL/min, respectively, are observed after injection of O1918 (3 µmol/kg). O1918 causes an inhibition of the anandamide-stimulated decreases in MBP, SBP and DBP by 55, 38 and 42% respectively. Similarly, this antagonist reduces the methanandamide-stimulated fall in SBP and DBP by 44 and 32%, respectively, and tends to diminish the decrease in MBP by 28%. O1918 also diminishes the fall in MBF and RBF induced by anandamide by 61 and 67% and that induced by methanandamide by 74 and 49% respectively. Cannabidiol does not affect basal cardiovascular parameters whereas O1918 decreases HR by about 15 beats/min and SBP, DBP and MBP by about 15 mmHg. In pithed rats anandamide (3 µmol/kg) causes only an increase in MBF and RBF. The anandamide-induced long-lasting fall in MBP, SBP and DBP is reduced by cannabidiol by 40-46% and by O-1918 by 55, 64 and 35, respectively^[1].