Annual review of pharmacology and toxicology
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Annu. Rev. Pharmacol. Toxicol. · Jan 2021
ReviewTargeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors.
Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (-)-trans-Δ9-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB1 receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.
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Annu. Rev. Pharmacol. Toxicol. · Jan 2019
ReviewOrganoids for Drug Discovery and Personalized Medicine.
A wide variety of organs are in a dynamic state, continuously undergoing renewal as a result of constant growth and differentiation. Stem cells are required during these dynamic events for continuous tissue maintenance within the organs. In a steady state of production and loss of cells within these tissues, new cells are constantly formed by differentiation from stem cells. ⋯ As they are similar to their original organs, organoids hold great promise for use in medical research and the development of new treatments. Furthermore, they have already been utilized in the clinic, enabling personalized medicine for inflammatory bowel disease. In this review, I provide an update on current organoid technology and summarize the application of organoids in basic research, disease modeling, drug development, personalized treatment, and regenerative medicine.
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The widespread abuse of prescription opioids and a dramatic increase in the availability of illicit opioids have created what is commonly referred to as the opioid epidemic. The magnitude of this epidemic is startling: About 4% of the adult US population misuses prescription opioids, and in 2015, more than 33,000 deaths were attributable to overdose with licit and illicit opioids. Increasing the availability of medication-assisted treatments (such as buprenorphine and naltrexone), the use of abuse-deterrent formulations, and the adoption of US Centers for Disease Control and Prevention prescribing guidelines all constitute short-term approaches to quell this epidemic. However, with more than 125 million Americans suffering from either acute or chronic pain, the development of effective alternatives to opioids, enabled at least in part by a fuller understanding of the neurobiological bases of pain, offers the best long-term solution for controlling and ultimately eradicating this epidemic.
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Despite the unprecedented Ebola virus outbreak response in West Africa, no Ebola medical countermeasures have been approved by the US Food and Drug Administration. However, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk-pathogen setting. Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (BCX4430, brincidofovir, favipiravir, and GS-5734), nucleic acid-based drugs (TKM-Ebola and AVI-7537), and immunotherapeutics (convalescent plasma and ZMapp). We review Ebola therapeutics progress in the aftermath of the West Africa Ebola virus outbreak and attempt to offer a glimpse of a path forward.
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Annu. Rev. Pharmacol. Toxicol. · Jan 2015
ReviewDREADDs (designer receptors exclusively activated by designer drugs): chemogenetic tools with therapeutic utility.
In the past decade, emerging synthetic biology technologies such as chemogenetics have dramatically transformed how pharmacologists and systems biologists deconstruct the involvement of G protein-coupled receptors (GPCRs) in a myriad of physiological and translational settings. Here we highlight a specific chemogenetic application that extends the utility of the concept of RASSLs (receptors activated solely by synthetic ligands): We have dubbed it DREADDs (designer receptors exclusively activated by designer drugs). ⋯ We also highlight recent applications of DREADD technology that have illuminated GPCR signaling processes that control pathways relevant to the treatment of eating disorders, obesity, and obesity-associated metabolic abnormalities. Additionally, we provide an overview of the potential utility of chemogenetic technologies for transformative therapeutics.