In vivo pharmacology of endocannabinoids and their metabolic inhibitors: Therapeutic implications in Parkinson's disease and abuse liability |
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| Authors: | Andrea Giuffrida Lance R. McMahon |
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| Affiliation: | 1. Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain;2. Division of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain;3. Small Molecule Discovery Platform, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain;4. Laboratory of Neuroimmunology, Fundación Ciencia y Vida, Santiago, Chile;5. Programa de Biomedicina, Universidad San Sebastián, Santiago, Chile;6. Neuroscience Research Center, Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA;7. Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain;8. Department of Biochemistry and Genetics, School of Science, University of Navarra, Pamplona, Spain;1. Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States;2. Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States;3. The Bert W. Strassburger Lipid Center, Tel Aviv University, 52621 Hashomer Tel, Israel;4. Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, 52621 Hashomer Tel, Israel;5. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, United States;1. Department of Systems Medicine, University of Rome, “Tor Vergata”, Rome, Italy;2. Faculty of Veterinary Medicine, University of Teramo, Italy;3. Department of Experimental Medicine & Surgery, University of Rome, “Tor Vergata”, Rome, Italy;4. Fondazione Santa Lucia, IRCCS, Rome, Italy;5. School of Medicine and Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy;1. Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;2. Department of Mediator and Signal Transduction Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;3. Department of Anatomy, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan;4. Department of Matrix Biology and Regenerative Medicine, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;1. Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada;2. Laboratory Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada;3. Department of Pharmacology, Faculty of Medicine, University of Toronto, ON, Canada |
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| Abstract: | This review focuses on the behavioral pharmacology of endogenous cannabinoids (endocannabinoids) and indirect-acting cannabinoid agonists that elevate endocannabinoid tone by inhibiting the activity of metabolic enzymes. Similarities and differences between prototype cannabinoid agonists, endocannabinoids and inhibitors of endocannabinoid metabolism are discussed in the context of endocannabinoid pharmacokinetics in vivo. The distribution and function of cannabinoid and non-CB1/CB2 receptors are also covered, with emphasis on their role in disorders characterized by dopamine dysfunction, such as drug abuse and Parkinson's disease. Finally, evidence is presented to suggest that FAAH inhibitors lack the abuse liability associated with CB1 agonists, although they may modify the addictive properties of other drugs, such as alcohol. |
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