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Overview
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Background
O-1821 is an cannabidiol analog with similar structure to O-1918, a selective antagonist of abnormal cannabidiol.
Abnormal cannabidiol, a synthetic regioisomer of cannabidiol, fails to elicit either central cannabinoid (CB1) or peripheral cannabinoid (CB2) receptors and is lack of psychotropic activity. It can induce endothelium-dependent vasodilation through a CB1/CB2/nitric oxide-independent mechanism.
In vitro: O-1821 is a cannabidiol analog with similar structure to O-1918, which was identified as a selective antagonist of abnormal cannabidiol at the non-central cannabinoid (CB1)/peripheral cannabinoid (CB2) receptors endothelial receptor. It was found that O-1918 could not bind to CB1 or CB2 receptors and thus could not cause vasorelaxation at concentrations up to 30 μM, but it could cause concentration-dependent inhibition of the vasorelaxant effects of abn-cbd and anandamide. Moreover, in human umbilical vein endothelial cells, abn-cbd was able to induce phosphorylation of p42/44 mitogenactivated protein kinase and protein kinase B/Akt, which could be inhibited by O-1918 or by phosphatidylinositol 3 (PI3) kinase inhibitors [1].
In vivo: O-1918 was found to be able to inhibit the hypotensive effect of abn-cbd dose-dependently but not the hypotensive effect of the CB1 receptor agonist (-)-11-OH-Δ9-tetrahydrocannabinol dimethylheptyl in anesthetized mice [1].
Clinical trial: So far, no clinical study has been conducted.
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