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 CB1 and CB2 receptors, the molecular targets for Δ9-tetrahydrocannabinol (Δ9-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. A variety of chemically diverse FAAH and MGL inhibitors have been developed and synthesized recently. Thus, this article reviews the scientific literature of various FAAH and MGL inhibitors presented during the past ten years.
Keywords: Endocannabinoids, Fatty acid amide hydrolase, Monoglyceride lipase, Monoacylglycerol lipase, N-arachidonoylethanolamine, 2-Arachidonoylglycerol
Current Topics in Medicinal Chemistry
Title: Discovery and Development of Endocannabinoid-Hydrolyzing Enzyme Inhibitors
Volume: 10 Issue: 8
Author(s): Anna Minkkila, Susanna M. Saario and Tapio Nevalainen
Affiliation:
Keywords: Endocannabinoids, Fatty acid amide hydrolase, Monoglyceride lipase, Monoacylglycerol lipase, N-arachidonoylethanolamine, 2-Arachidonoylglycerol
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 CB1 and CB2 receptors, the molecular targets for Δ9-tetrahydrocannabinol (Δ9-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. A variety of chemically diverse FAAH and MGL inhibitors have been developed and synthesized recently. Thus, this article reviews the scientific literature of various FAAH and MGL inhibitors presented during the past ten years.
Export Options
About this article
Cite this article as:
Minkkila Anna, M. Saario Susanna and Nevalainen Tapio, Discovery and Development of Endocannabinoid-Hydrolyzing Enzyme Inhibitors, Current Topics in Medicinal Chemistry 2010; 10 (8) . https://dx.doi.org/10.2174/156802610791164238
DOI https://dx.doi.org/10.2174/156802610791164238 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Natural Monophenols as Therapeutics, Antioxidants and Toxins; Electron Transfer, Radicals and Oxidative Stress
The Natural Products Journal Recent Advances in the Design and Synthesis of SH2 Inhibitorsof Src, Grb2 and ZAP-70.
Current Medicinal Chemistry The Role of Mass Spectrometry in the “Omics” Era
Current Organic Chemistry Targeting Cancer Using Fragment Based Drug Discovery
Anti-Cancer Agents in Medicinal Chemistry A Novel Fluorescence-Labeled Curcumin Conjugate: Synthesis, Evaluation and Imaging on Human Cell Lines
Current Pharmaceutical Design CA125: An Increasingly Promising Biomarker of Heart Failure
Current Pharmaceutical Design Serum of Blood Separation by Means of Dynamic Electrochromatography in a Centrifugal and Electromagnetic Gradient
Recent Patents on Biotechnology The Misuse of Prescription Opioids: A Threat for Europe?
Current Drug Abuse Reviews Hybrid PET/MRI for In Vivo Imaging of Cancer: Current Clinical Experiences and Recent Advances
Current Medical Imaging <i>Prunella vulgaris</i> L: Critical Pharmacological, Expository Traditional Uses and Extensive Phytochemistry: A Review
Current Drug Discovery Technologies Iontophoretic Mediated Intraarticular Delivery of Deformable Liposomes of Diclofenac Sodium
Current Drug Delivery The Use of Intravenous Aminobisphosphonates for the Treatment of Pagets Disease of Bone
Mini-Reviews in Medicinal Chemistry Interactions of Polyphenols with Plasma Proteins: Insights from Analytical Techniques
Current Drug Metabolism Using Mass Spectrometry-Based Peptidomics to understand the Brain and Disorders such as Parkinson’s Disease and Schizophrenia
Current Topics in Medicinal Chemistry Discover Patent Landscape of Two-photon Polymerization Technology for the Production of 3D Nano-structure Using Claim-based Approach
Recent Patents on Nanotechnology Calpains: Attractive Targets for the Development of Synthetic Inhibitors
Current Topics in Medicinal Chemistry <i>Solanum pubescens</i> Wild Fruits Essential Oil - A Golden Casket for its Antimicrobial and Anti-inflammatory Mediated Wound Healing Efficacy in Vertebrate Model <i>Mus musculus</i>
Current Topics in Medicinal Chemistry In Vivo Tumor Secretion Probing Via Ultrafiltration and Tissue Chamber:Implication for Anti-Cancer Drugs Targeting Secretome
Recent Patents on Anti-Cancer Drug Discovery In Vitro and In Vivo Models for Analysis of Resistance to Anticancer Molecular Therapies
Current Medicinal Chemistry Polyphenols Beyond Barriers: A Glimpse into the Brain
Current Neuropharmacology