Therapeutic potential of the endocannabinoid system in the brain.
Cannabinoids have been predominantly considered as the substances responsible of the psychoactive properties of marijuana and other derivatives of Cannabis sativa. However, these compounds are now being also considered for their therapeutic potential, since the term "cannabinoid" includes much more compounds than those present in Cannabis sativa derivatives. Among them, there are numerous synthetic cannabinoids obtained by modifications from plant-derived cannabinoids, but also from the compounds that behave as endogenous ligands for the different cannabinoid receptor subtypes. Within the family of "cannabinoid-related compounds", one should also include some prototypes of selective antagonists for these receptors, and also the recently developed inhibitors of the mechanism of finalization of the biological action of endocannabinoids (transporter + FAAH). All this boom of the cannabinoid pharmacology has, therefore, an explanation in the recent discovery and characterization of the endocannabinoid signaling system, which plays a modulatory role mainly in the brain but also in the periphery. The objective of the present article will be to review, from pharmacological and biochemical points of view, the more recent advances in the study of the endocannabinoid system and their functions in the brain, as well as their alterations in a variety of pathologies and the proposed therapeutic benefits of novel cannabinoid-related compounds that improve the pharmacokinetic and pharmacodynamic properties of classic cannabinoids.
Ramos
José Antonio
JA
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain. jara@med.ucm.es
González
Sara
S
Sagredo
Onintza
O
Gómez-Ruiz
María
M
Fernández-Ruiz
Javier
J
D000581:Amidohydrolases / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002188:Cannabis / Q000378:metabolism*; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000187:drug effects* / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D043882:Receptors, Cannabinoid; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate