Abstract
Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) are hydrolytic enzymes which degrade the endogenous cannabinoids (endocannabinoids) N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), respectively. Endocannabinoids are an important class of lipid messenger molecules that are produced on demand in response to elevated intracellular calcium levels. They recognize and activate the cannabinoid CB(1) and CB(2) receptors, the molecular targets for Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in marijuana evoking several beneficial therapeutic effects. However, in vivo the cannabimimetic effects of AEA and 2-AG remain weak owing to their rapid inactivation by FAAH and MGL, respectively. The inactivation of FAAH and MGL by specific enzyme inhibitors increases the levels of AEA and 2-AG, respectively, producing therapeutic effects such as pain relief and depression of anxiety.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amidohydrolases / antagonists & inhibitors
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Amidohydrolases / metabolism
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Arachidonic Acids / metabolism
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Cannabinoid Receptor Modulators / chemistry
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Cannabinoid Receptor Modulators / pharmacology*
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Cannabinoid Receptor Modulators / therapeutic use
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Dronabinol / analogs & derivatives
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Dronabinol / metabolism
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Endocannabinoids*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / therapeutic use
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Glycerides / metabolism
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Humans
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Monoacylglycerol Lipases / antagonists & inhibitors
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Monoacylglycerol Lipases / metabolism
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Nervous System Diseases / drug therapy
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Nervous System Diseases / pathology
Substances
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Arachidonic Acids
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Cannabinoid Receptor Modulators
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Endocannabinoids
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Enzyme Inhibitors
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Glycerides
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11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid
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Dronabinol
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glyceryl 2-arachidonate
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Monoacylglycerol Lipases
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Amidohydrolases
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fatty-acid amide hydrolase