The endogenous cannabinoid system and the basal ganglia. biochemical, pharmacological, and therapeutic aspects.
New data strengthen the idea of a prominent role for endocannabinoids in the modulation of a wide variety of neurobiological functions. Among these, one of the most important is the control of movement. This finding is supported by 3 lines of evidence: (1) the demonstration of a powerful action, mostly inhibitory in nature, of synthetic and plant-derived cannabinoids and, more recently, of endocannabinoids on motor activity; (2) the presence of the cannabinoid CB(1) receptor subtype and the recent description of endocannabinoids in the basal ganglia and the cerebellum, the areas that control movement; and (3) the fact that CB(1) receptor binding was altered in the basal ganglia of humans affected by several neurological diseases and also of rodents with experimentally induced motor disorders. Based on this evidence, it has been suggested that new synthetic compounds that act at key steps of endocannabinoid activity (i.e., more-stable analogs of endocannabinoids, inhibitors of endocannabinoid reuptake or metabolism, antagonists of CB(1) receptors) might be of interest for their potential use as therapeutic agents in a variety of pathologies affecting extrapyramidal structures, such as Parkinson's and Huntington's diseases. Currently, only a few data exist in the literature studying such relationships in humans, but an increasing number of journal articles are revealing the importance of this new neuromodulatory system and arguing in favour of the funding of more extensive research in this field. The present article will review the current knowledge of this neuromodulatory system, trying to establish the future lines for research on the therapeutic potential of the endocannabinoid system in motor disorders.
Laboratorio de Apoyo a la Investigación, Fundación Hospital Alcorcón, Madrid, Spain.
Julián
J
Romero
Isabel
I
Lastres-Becker
Rosario
R
de Miguel
Fernando
F
Berrendero
José A
JA
Ramos
Javier
J
Fernández-Ruiz
D000375:Aging / Q000502:physiology; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D009069:Movement Disorders / Q000188:drug therapy / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000523:psychology; D018377:Neurotransmitter Agents / Q000378:metabolism; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D005231:Fatty Acids, Unsaturated; D018377:Neurotransmitter Agents; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug