Review
Biochemistry & Molecular Biology
Dorsa Rafiei, Nathan J. Kolla
Summary: Studies have shown that increased FAAH expression is significantly correlated with depressive-like behaviors in animal models, and genetic knockout or pharmacological inhibition of FAAH can effectively reduce these behaviors in a dose-dependent manner. Differences in FAAH expression in depressive-like phenotypes are mainly localized in the animal prefrontal cortex, hippocampus, and striatum. Based on this, FAAH is considered a promising target for developing new pharmacotherapies for Major Depressive Disorder (MDD).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tiziana Genovese, Andrea Duranti, Ramona D'Amico, Roberta Fusco, Daniela Impellizzeri, Alessio Filippo Peritore, Rosalia Crupi, Enrico Gugliandolo, Salvatore Cuzzocrea, Rosanna Di Paola, Rosalba Siracusa, Marika Cordaro
Summary: Acute lung injury (ALI) is a lung disease characterized by severe inflammation without treatment. This study investigated the role of fatty acid amide hydrolase (FAAH) inhibition in an ALI mouse model and found that it could counteract the inflammatory response and histological changes caused by the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Medicinal
Shivani Jaiswal, Senthil Raja Ayyannan
Summary: Recently, FAAH and MAGL inhibitors have attracted attention for their potential anticancer effects. By regulating endogenous ligands, these inhibitors show therapeutic effects in chronic pain, metabolic disorders, psychoses, among others, and exhibit potential in various types of cancers.
Article
Pharmacology & Pharmacy
Anitha Police, Vijay Kumar Shankar, Pankaj Pandey, Srinath Rangappa, Robert J. Doerksen, S. Narasimha Murthy
Summary: Peripheral neuropathy (PN) is a condition characterized by peripheral nerve damage leading to severe pain. The current treatments for PN have either psychotropic side effects or are not effective enough. This study aims to find a safe inhibitor of the fatty acid amide hydrolase enzyme (FAAH) and develop a topical gel formulation to deliver anandamide, an endocannabinoid that relieves PN pain. The results showed that silymarin constituents, particularly silybin, demonstrated significant FAAH inhibition potential and increased the half-life of anandamide. The developed gel formulation increased the permeation of anandamide and silybin, resulting in a significant increase in pain threshold in rat models of PN.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Marek Zubrzycki, Maria Zubrzycka, Grzegorz Wysiadecki, Janusz Szemraj, Hanna Jerczynska, Mariusz Stasiolek
Summary: This study assessed the effects of fatty acid amide hydrolase inhibitor URB597 in an animal model of orofacial pain caused by tooth pulp stimulation. The results showed that URB597, by inhibiting the metabolism of endocannabinoids and reducing gene expression levels, effectively prevented orofacial pain, providing a promising therapeutic target for its treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Shirley Alteba, Anna Portugalov, Cecilia J. Hillard, Irit Akirav
Summary: Early-life stress and early cannabis use may increase the risk of psychopathologies, affecting behavior in male and female rats. Chronic FAAH inhibition during mid-adolescence did not prevent the long-term effects of ELS on behavior, while it ameliorated ELS-induced depression and anxiety-like behavior during late-adolescence. Sex-dependent alterations in CB1 receptors and GRs expression in the BLA-PFC-CA1 circuit may contribute to the depressive behavioral phenotype.
Article
Neurosciences
Yannick Fotio, Alex Mabou Tagne, Kwang-Mook Jung, Daniele Piomelli
Summary: In this study, the effects of two novel brain-permeable FAAH inhibitors, ARN14633 and ARN14280, were investigated in a rat model of predator stress-induced long-term anxiety. The results showed that these inhibitors effectively reduced anxiety-like behaviors and were correlated with the inhibition of FAAH activity and increase in FAAH substrate levels. This study supports the potential clinical application of FAAH inhibitors in the management of PTSD.
PSYCHOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Anca Zanfirescu, Georgiana Nitulescu, Dragos Paul Mihai, George Mihai Nitulescu
Summary: Chronic pain poses a significant burden on individuals, employers, healthcare systems, and society, and current treatment options are often unsatisfactory. Through screening and research methods, we have identified several repurposable drugs that show promise for treating chronic pain.
Article
Anesthesiology
Diana Amorim, Diana Fonseca-Rodrigues, Ana David-Pereira, Octavia Costa, Antonia Palhares Lima, Rosete Nogueira, Rute Cruz, Ana Sofia Martins, Liliana Sousa, Francisco Oliveira, Helder Pereira, Rogerio Pirraco, Antti Pertovaara, Armando Almeida, Filipa Pinto-Ribeiro
Summary: The injection of kaolin/carrageenan in the rat knee joint successfully models the physical and psychiatric features of human osteoarthritis. This experimental osteoarthritis allows for the study of disease mechanisms and evaluation of therapeutic strategies to halt disease progression at different stages.
Article
Chemistry, Multidisciplinary
Stefan Rudolph, Helmut Dahlhaus, Walburga Hanekamp, Christian Albers, Maximilian Barth, Giulia Michels, Denise Friedrich, Matthias Lehr
Summary: A series of aryl N-[omega-(6-fluoroindol-1-yl)alkyl]-carbamates were synthesized and tested for inhibition of several important serine hydrolases. Most of the synthesized derivatives showed strong inhibition of FAAH, while some compounds also exhibited good inhibition of MAGL and BuChE. Some carbamates showed varying degrees of stability or inactivation towards esterases, with some forming covalent bonds with albumin.
Article
Biochemistry & Molecular Biology
Shivani Jaiswal, Akhilesh, Ankit Uniyal, Vinod Tiwari, Senthil Raja Ayyannan
Summary: Researchers have discovered a promising lead compound for the treatment of neuropathic pain by designing and synthesizing a series of compounds. The lead compound exhibited potent inhibition activity against both FAAH and MAGL, and showed good safety profile in vivo experiments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Chaoling Chen, Weili Wang, Justin L. Poklis, Aron H. Lichtman, Joseph K. Ritter, Gaizun Hu, Dengpiao Xie, Ningjun Li
Summary: The study suggests that FAAH activation and the consequent reduction of AEA contribute to renal fibrogenesis, while FAAH inhibition protects against fibrogenesis in renal cells independently of CB receptors via the AEA-COX-2 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Sanela Rajlic, Luise Surmann, Pia Zimmermann, Christina Katharina Weisheit, Laura Bindila, Hendrik Treede, Markus Velten, Andreas Daiber, Georg Daniel Duerr
Summary: Ischemic cardiomyopathy leads to inflammation and left ventricular dysfunction. Animal studies suggest that the endocannabinoid system may have cardioprotective effects, including cardiomyocyte adaptation, inflammation, and remodeling. This study investigates the potential cardioprotective effect of the endocannabinoid anandamide (AEA) after ischemia and reperfusion using FAAH (-/-) mice and suggests that increased endocannabinoids may have detrimental effects on cardiomyocyte survival due to PPAR-alpha activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Veterinary Sciences
Vikram Thakur, Mohammad Bashashati, Josue Enriquez, Munmun Chattopadhyay
Summary: This study assessed specific gastrointestinal symptoms in Type 1 diabetic mice and evaluated treatment options for this condition. The results showed that inhibiting endocannabinoid degradation may have a therapeutic effect on gastrointestinal dysmotility.
VETERINARY SCIENCES
(2022)
Review
Orthopedics
M. Alves-Simoes
Summary: This review provides an overview of current models used for studying osteoarthritis (OA) pain, focusing on mice and rats. The article emphasizes that although there is no ideal model for studying OA pain, increased efforts in phenotyping OA will impact the choice of models for pre-clinical and basic research studies.
OSTEOARTHRITIS AND CARTILAGE
(2022)
Article
Immunology
Milind M. Muley, Eugene Krustev, Allison R. Reid, Jason J. McDougall
JOURNAL OF NEUROINFLAMMATION
(2017)
Article
Endocrinology & Metabolism
Eugene Krustev, Milind M. Muley, Jason J. McDougall
Article
Orthopedics
J. J. McDougall, S. Albacete, N. Schuelert, P. G. Mitchell, C. Lin, J. L. Oskins, H. H. Bui, M. G. Chambers
OSTEOARTHRITIS AND CARTILAGE
(2017)
Article
Anesthesiology
Holly T. Philpott, Melissa O'Brien, Jason J. McDougall
Review
Rheumatology
Kai Fu, Sarah R. Robbins, Jason J. McDougall
Article
Behavioral Sciences
L. D. Ellis, F. Berrue, M. Morash, J. C. Achenbach, J. Hill, J. J. McDougall
BEHAVIOURAL BRAIN RESEARCH
(2018)
Article
Pharmacology & Pharmacy
Melissa O'Brien, Jason J. McDougall
CURRENT OPINION IN PHARMACOLOGY
(2018)
Article
Orthopedics
R. Pujol, C. A. Girard, H. Richard, I. Hassanpour, M. P. Binette, G. Beauchamp, J. J. McDougall, S. Laverty
OSTEOARTHRITIS AND CARTILAGE
(2018)
Article
Multidisciplinary Sciences
Ramin Goudarzi, Allison Reid, Jason J. McDougall
Article
Anesthesiology
Melissa S. O'Brien, Holly T. A. Philpott, Jason J. McDougall
Article
Multidisciplinary Sciences
Michael Mousseau, Nicole E. Burma, Kwan Yeop Lee, Heather Leduc-Pessah, Charlie H. T. Kwok, Allison R. Reid, Melissa O'Brien, Boriss Sagalajev, Jo Anne Stratton, Natalya Patrick, Patrick L. Stemkowski, Jeff Biernaskie, Gerald W. Zamponi, Paul Salos, Jason J. McDougall, Steven A. Prescott, John R. Matyas, Tuan Trang
Article
Cell Biology
Melissa S. O'Brien, Jason J. McDougall
MECHANISMS OF AGEING AND DEVELOPMENT
(2019)
Review
Biochemistry & Molecular Biology
Flora Lucena, Jason J. McDougall
Summary: Serine proteases play a dual role in arthritic joints by not only causing destruction but also signaling pain and inflammation. Protease activated receptors (PARs) have the potential to regulate joint homeostasis and targeting them may offer therapeutic benefits for alleviating pain and destructive nature of elevated proteases in arthritis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Rheumatology
Holly T. Philpott, Jason J. McDougall
ARTHRITIS RESEARCH & THERAPY
(2020)
Article
Rheumatology
Jason J. McDougall, Milind M. Muley, Holly T. Philpott, Allison Reid, Eugene Krustev
ARTHRITIS RESEARCH & THERAPY
(2017)