Targeting Cannabinoid CB(2) Receptors in the Central Nervous System. Medicinal Chemistry Approaches with Focus on Neurodegenerative Disorders

Endocannabinoids activate two types of specific G-protein-coupled receptors (GPCRs), namely cannabinoid CB(1) and CB(2). Contrary to the psychotropic actions of agonists of CB(1) receptors, and serious side effects of the selective antagonists of this receptor, drugs acting on CB(2) receptors appear as promising drugs to combat CNS diseases (Parkinson's disease, Huntington's chorea, cerebellar ataxia, amyotrohic lateral sclerosis). Differential localization of CB(2) receptors in neural cell types and upregulation in neuroinflammation are keys to understand the therapeutic potential in inter alia diseases that imply progressive neurodegeneration. Medicinal chemistry approaches are now engaged to develop imaging tools to map receptors in the living human brain, to develop more efficacious agonists, and to investigate the possibility to develop allosteric modulators.