Tags

Type your tag names separated by a space and hit enter

FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels.
Curr Opin Investig Drugs 2010; 11(1):51-62CO

Abstract

Apart from their widespread recreational abuse, the psychoactive preparations of the plant Cannabis sativa and its major psychotropic component, Delta9-tetrahydrocannabinol (THC), are also known for their medicinal properties. Following the identification of receptors for THC - the cannabinoid CB1 and CB2 receptors - in mammals, various pharmaceutical strategies have attempted to exploit the properties of the cannabinoid system while minimizing psychotropic side effects. The cloning of the cannabinoid CB1 and CB2 receptors enabled the discovery of the endogenous agonists of the receptors, the endocannabinoids, and eventually led to the identification of enzymes that catalyze endocannabinoid inactivation. Unlike exogenously administered THC and synthetic CB1 and CB2 agonists, the endocannabinoids that are produced endogenously following the onset of several pathologies may act in a site- and time-specific manner to minimize the consequences of such conditions. This observation has suggested the possibility of targeting endocannabinoid-degrading enzymes to prolong the precisely regulated pro-homeostatic action of endocannabinoids. Two major enzymes have been cloned and investigated thoroughly: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Inhibitors of these enzymes have demonstrated therapeutic benefit in animal models of several disorders, including neuropathic pain, anxiety and inflammatory bowel diseases, as well as against the proliferation and migration of cancer cells. This review describes the major biochemical properties of FAAH and MAGL, and the design and pharmacological properties of inhibitors of these enzymes.

Authors+Show Affiliations

Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34, 80078, Pozzuoli, Naples, Italy.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

20047159

Citation

Petrosino, Stefania, and Vincenzo Di Marzo. "FAAH and MAGL Inhibitors: Therapeutic Opportunities From Regulating Endocannabinoid Levels." Current Opinion in Investigational Drugs (London, England : 2000), vol. 11, no. 1, 2010, pp. 51-62.
Petrosino S, Di Marzo V. FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. Curr Opin Investig Drugs. 2010;11(1):51-62.
Petrosino, S., & Di Marzo, V. (2010). FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. Current Opinion in Investigational Drugs (London, England : 2000), 11(1), pp. 51-62.
Petrosino S, Di Marzo V. FAAH and MAGL Inhibitors: Therapeutic Opportunities From Regulating Endocannabinoid Levels. Curr Opin Investig Drugs. 2010;11(1):51-62. PubMed PMID: 20047159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. AU - Petrosino,Stefania, AU - Di Marzo,Vincenzo, PY - 2010/1/5/entrez PY - 2010/1/5/pubmed PY - 2010/3/24/medline SP - 51 EP - 62 JF - Current opinion in investigational drugs (London, England : 2000) JO - Curr Opin Investig Drugs VL - 11 IS - 1 N2 - Apart from their widespread recreational abuse, the psychoactive preparations of the plant Cannabis sativa and its major psychotropic component, Delta9-tetrahydrocannabinol (THC), are also known for their medicinal properties. Following the identification of receptors for THC - the cannabinoid CB1 and CB2 receptors - in mammals, various pharmaceutical strategies have attempted to exploit the properties of the cannabinoid system while minimizing psychotropic side effects. The cloning of the cannabinoid CB1 and CB2 receptors enabled the discovery of the endogenous agonists of the receptors, the endocannabinoids, and eventually led to the identification of enzymes that catalyze endocannabinoid inactivation. Unlike exogenously administered THC and synthetic CB1 and CB2 agonists, the endocannabinoids that are produced endogenously following the onset of several pathologies may act in a site- and time-specific manner to minimize the consequences of such conditions. This observation has suggested the possibility of targeting endocannabinoid-degrading enzymes to prolong the precisely regulated pro-homeostatic action of endocannabinoids. Two major enzymes have been cloned and investigated thoroughly: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Inhibitors of these enzymes have demonstrated therapeutic benefit in animal models of several disorders, including neuropathic pain, anxiety and inflammatory bowel diseases, as well as against the proliferation and migration of cancer cells. This review describes the major biochemical properties of FAAH and MAGL, and the design and pharmacological properties of inhibitors of these enzymes. SN - 2040-3429 UR - https://www.unboundmedicine.com/medline/citation/20047159/FAAH_and_MAGL_inhibitors:_therapeutic_opportunities_from_regulating_endocannabinoid_levels_ DB - PRIME DP - Unbound Medicine ER -