The Inhibitory Effect of S-777469, a Cannabinoid Type 2 Receptor Agonist, on Skin Inflammation in Mice.

“We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4-fluorobenzyl]-5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl]amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The oral administration of S-777469 significantly suppressed DNFB-induced ear swelling in a dose-dependent manner. In addition, S-777469 significantly alleviated mite antigen-induced atopic dermatitis-like skin lesions in NC/Nga mice. A histological analysis revealed that S-777469 significantly reduced the epidermal thickness and the number of mast cells infiltrating skin lesions. We demonstrated that S-777469 inhibited mite antigen-induced eosinophil accumulation in skin lesions and an endogenous CB2 ligand, 2-arachidonoylglycerol (2-AG)-induced eosinophil migration in vitro. Moreover, we confirmed that 2-AG levels significantly increased in skin lesions of mite antigen-induced dermatitis model. Together, these results suggest that S-777469 inhibits skin inflammation in mice by blocking the activities of 2-AG.” https://www.ncbi.nlm.nih.gov/pubmed/28214870]]>

Brain cannabinoid systems as targets for the therapy of neurological disorders.

Image result for Neurobiology of Disease “Unprecedented developments in cannabinoid research within the past decade include discovery of a brain (CB1) and peripheral (CB2) receptor; endogenous ligands, anandamide, and 2-arachidonylglycerol; cannabinoid drug-induced partial and inverse agonism at CB1 receptors, antagonism of NMDA receptors and glutamate, and antioxidant activity; and preferential CB1 receptor localization in areas subserving spasticity, pain, abnormal involuntary movements, seizures, and amnesia. These endogenous structures and chemicals and mechanisms are potentially new pathophysiologic substrates, and targets for novel cannabinoid treatments, of several neurological disorders.” https://www.ncbi.nlm.nih.gov/pubmed/9974182 
“Endocannabinoid System in Neurological Disorders.” https://www.ncbi.nlm.nih.gov/pubmed/27364363
“Cannabinoids in the Treatment of Neurological Disorders” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604187/
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