cannabidiol and ammonium-acetate

Cannabidiol (CBD) exhibits neuroprotective properties in many experimental systems. However, development of CBD as a drug has been confounded by the following: (1) low potency; (2) a large number of molecular targets; (3) marginal pharmacokinetic properties; and (4) designation as a schedule 1 controlled substance. The present work compared the properties of CBD with a novel molecule (KLS-13019) that has structural similarities to CBD. The design strategy for KLS-13019 was to increase hydrophilicity while optimizing neuroprotective potency against oxidative stress toxicity relevant to hepatic encephalopathy. The protective responses of CBD and KLS-13019 were compared in dissociated rat hippocampal cultures co-treated with toxic levels of ethanol and ammonium acetate. This comparison revealed that KLS-13019 was 31-fold more potent than CBD in preventing neuronal toxicity from the combined toxin treatment, while both compounds exhibited complete protective efficacy back to control values. In addition, treatment with KLS-13019 alone was 5-fold less toxic (TC50) than CBD. Previous studies suggested that CBD targeted the Na

Topics: Acetates; Animals; Cannabidiol; Cells, Cultured; Ethanol; Hippocampus; Neurons; Neuroprotective Agents; Rats; Sodium-Calcium Exchanger