Enol Carbamates as Inhibitors of Fatty Acid Amide Hydrolase (FAAH) Endowed with High Selectivity for FAAH over the Other Targets of the Endocannabinoid System

ChemMedChem ◽  
2010 ◽  
Vol 5 (3) ◽  
pp. 357-360 ◽  
Author(s):  
Sonia Gattinoni ◽  
Chiara De Simone ◽  
Sabrina Dallavalle ◽  
Filomena Fezza ◽  
Raffaella Nannei ◽  
...  
Keyword(s):  
Fatty Acid ◽  
High Selectivity ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
The Other ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

2021 ◽  
Vol 22 (3) ◽  
pp. 1047
Author(s):  
Dorsa Rafiei ◽  
Nathan J. Kolla
Keyword(s):  
Depressive Symptoms ◽  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Animal Models Of Depression ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

Fatty Acid Amide Hydrolase Inhibitors from Virtual Screening of the Endocannabinoid System

2006 ◽  
Vol 49 (15) ◽  
pp. 4650-4656 ◽  
Author(s):  
Susanna M. Saario ◽  
Antti Poso ◽  
Risto O. Juvonen ◽  
Tomi Järvinen ◽  
Outi M. H. Salo-Ahen
Keyword(s):  
Fatty Acid ◽  
Virtual Screening ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Equipotent Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase – Dual Targets of the Endocannabinoid System to Protect against Seizure Pathology

2012 ◽  
Vol 9 (4) ◽  
pp. 801-813 ◽  
Author(s):  
Vinogran Naidoo ◽  
David A. Karanian ◽  
Subramanian K. Vadivel ◽  
Johnathan R. Locklear ◽  
JodiAnne T. Wood ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Monoacylglycerol Lipase ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Endocannabinoid System: Overview and Therapeutic Relevance

2021 ◽  
Author(s):  
Alex Mabou Tagne
Keyword(s):  
Fatty Acid ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Receptor Subtypes ◽  
Monoacylglycerol Lipase ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

The endocannabinoid system (ECS) modulates a variety of physiological processes, attracting considerable attention as a potential target for therapeutic intervention. This complex system is activated by the lipid-derived mediators anandamide and 2-arachidonoyl-sn-glycerol (2-AG), which mainly engage the cannabinoid receptor subtypes 1 (CB1) and 2 (CB2). The biological actions of anandamide and 2-AG are terminated by internalization and intracellular enzymatic hydrolysis catalyzed primarily by the serine hydrolases fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL), respectively. Here, we provide an overview of ECS and discuss the implications for advancing pharmacological tools that interfere with such a system as next-generation therapeutics. This review contains 4 figures, 3 tables and 41 references Keywords: Endocannabinoid; anandamide; 2-Arachidonoyl-sn-glycerol; fatty acid amide hydrolase; monoacylglycerol lipase; cannabinoid receptors; N-acylethanolamine acid amidase; Δ9-tetrahydrocannabinol.

Effects of General Anesthesia on Anandamide Blood Levels in Humans

2006 ◽  
Vol 104 (2) ◽  
pp. 273-277 ◽  
Author(s):  
Gustav Schelling ◽  
Daniela Hauer ◽  
Shahnaz Christina Azad ◽  
Martin Schmoelz ◽  
Alexander Chouker ◽  
...  
Keyword(s):  
Fatty Acid ◽  
General Anesthesia ◽  
Repeated Measures ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Blood Levels ◽  
General Anesthetics ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Background The endocannabinoid system includes G-protein-coupled cannabinoid receptors, the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, and multiple enzymes involved in the biosynthesis and degradation of endocannabinoids, including the anandamide metabolizing enzyme fatty acid amide hydrolase. Endocannabinoids play an important role in the physiologic control of sleep, pain processing, and emesis. The authors therefore investigated the effects of general anesthesia on the endocannabinoid system in humans. Methods The authors measured whole blood levels of anandamide in 12 patients after induction of general anesthesia with etomidate (an agent shown to have no effect on anandamide levels) and maintenance of anesthesia with the volatile agent sevoflurane as well as in 12 patients undergoing total intravenous anesthesia with propofol, a known inhibitor of fatty acid amide hydrolase in the mouse brain. Anandamide levels were measured using high-performance liquid chromatography-tandem mass spectrometry at four time points (before and at 10, 20, 30, and 40 min after induction of anesthesia). Results Patients of the sevoflurane group showed a significant decline in anandamide levels from induction of anesthesia to 40 min after induction, whereas anandamide levels in patients of the propofol group remained unchanged (type III sum of squares = 1725.66, F = 162.60, P < 0.001, repeated-measures analysis of variance). Conclusion General anesthesia influences the endocannabinoid system in a drug-dependent way, which may explain side effects of general anesthetics such as psychomimetic and antiemetic properties of propofol and the high incidence of postoperative nausea and vomiting after volatile anesthetics. These findings suggest new targets for anesthetic drug development.

Modulation of the Endocannabinoid System via Inhibition of Fatty Acid Amide Hydrolase (FAAH) by Novel Urea and Carbamate Derivatives

2019 ◽  
Vol 4 (39) ◽  
pp. 11609-11614 ◽  
Author(s):  
Sarah Cramer ◽  
Jacklyn Johnson ◽  
Thanh Ngo ◽  
Abir T. El‐Alfy ◽  
Jozef Stec
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Amide Hydrolase ◽  
Fatty Acid Amide
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