title: Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis.
abstract: COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependent manner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines from normal healthy subjects and patients with relapsing-remitting multiple sclerosis (MS). In MS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanism involving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines. COR167 was also able to reduce in vitro migration of stimulated immunocompetent cells through human brain endothelium associated with a significant reduction of levels of several chemokines. These findings demonstrate that COR167 exerts potent immunomodulatory effects and confirm the cannabinoid CB2 receptor as a novel pharmacological target to counteract neuroinflammation.
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. Electronic address: annunziata@unisi.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Annunziata
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cioni
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mugnaini
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Corelli
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D063386:Cannabinoid Receptor Agonists; D016207:Cytokines; D007155:Immunologic Factors; C580859:N-(adamantan-1-yl)-4-oxo-1-pentyl-6-phenyl-1,4-dihydroquinoline-3-carboxamide; D015363:Quinolones; D043885:Receptor, Cannabinoid, CB2; D000218:Adamantane
keywords: CB2 receptor; Cannabinoids; Multiple sclerosis; Neuroimmunomodulation; Neuroinflammation