样式: 排序: IF: - GO 导出 标记为已读
-
Alcohol Use Disorder Treatment: Problems and Solutions Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2024-01-23 George F. Koob
Alcohol use disorder (AUD) afflicts over 29 million individuals and causes more than 140,000 deaths annually in the United States. A heuristic framework for AUD includes a three-stage cycle—binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation—that provides a starting point for exploring the heterogeneity of AUD with regard to treatment. Effective behavioral health treatments
-
Addressing Ancestry and Sex Bias in Pharmacogenomics Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2024-01-23 Manuel Corpas, Moneeza K. Siddiqui, Opeyemi Soremekun, Rohini Mathur, Dipender Gill, Segun Fatumo
The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain
-
Introduction to the Theme “Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment” Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-10-16 Urs A. Meyer, Susan G. Amara, Terrence F. Blaschke, Paul A. Insel
The reviews in Volume 64 of the Annual Review of Pharmacology and Toxicology cover diverse topics. A common theme in many of the reviews is the interindividual variability in the clinical response to drugs. Highlighted areas include emerging developments in pharmacogenomics that can predict the personal risk for drug inefficacy and/or adverse drug reactions. Other reviews focus on the use of circulating
-
Introduction to the Theme “Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment” Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-10-10 Urs A. Meyer, Susan G. Amara, Terrence F. Blaschke, Paul A. Insel
The reviews in Volume 64 of the Annual Review of Pharmacology and Toxicology cover diverse topics. A common theme in many of the reviews is the interindividual variability in the clinical response to drugs. Highlighted areas include emerging developments in pharmacogenomics that can predict the personal risk for drug inefficacy and/or adverse drug reactions. Other reviews focus on the use of circulating
-
Gene-Environment Interactions: My Unique Journey Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-10-03 Daniel W. Nebert
I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have authored/coauthored more than 600 publications in the fields of clinical medicine, biochemistry, biophysics, pharmacology, drug metabolism, toxicology, molecular biology, cancer, standardized gene nomenclature, developmental toxicology and teratogenesis
-
Anthracycline Toxicity: Light at the End of the Tunnel? Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-10-03 Romina B. Cejas, Kateryna Petrykey, Yadav Sapkota, Paul W. Burridge
Anthracycline-induced cardiotoxicity (AIC) is a serious and common side effect of anthracycline therapy. Identification of genes and genetic variants associated with AIC risk has clinical potential as a cardiotoxicity predictive tool and to allow the development of personalized therapies. In this review, we provide an overview of the function of known AIC genes identified by association studies and
-
Antiepileptic Drugs as Potential Dementia Prophylactics Following Traumatic Brain Injury Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-10-03 Laszlo F. Locskai, Hadeel Alyenbaawi, W. Ted Allison
Seizures and other forms of neurovolatility are emerging as druggable prodromal mechanisms that link traumatic brain injury (TBI) to the progression of later dementias. TBI neurotrauma has both acute and long-term impacts on health, and TBI is a leading risk factor for dementias, including chronic traumatic encephalopathy and Alzheimer's disease. Treatment of TBI already considers acute management
-
Oral Anticoagulants Beyond Warfarin Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-27 Renske H. Olie, Kristien Winckers, Bianca Rocca, Hugo ten Cate
Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently
-
Artificial Intelligence for Drug Discovery: Are We There Yet? Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-22 Catrin Hasselgren, Tudor I. Oprea
Drug discovery is adapting to novel technologies such as data science, informatics, and artificial intelligence (AI) to accelerate effective treatment development while reducing costs and animal experiments. AI is transforming drug discovery, as indicated by increasing interest from investors, industrial and academic scientists, and legislators. Successful drug discovery requires optimizing properties
-
Mass Spectrometry–Based Proteogenomics: New Therapeutic Opportunities for Precision Medicine Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-22 Sunil K. Joshi, Paul Piehowski, Tao Liu, Sara J.C. Gosline, Jason E. McDermott, Brian J. Druker, Elie Traer, Jeffrey W. Tyner, Anupriya Agarwal, Cristina E. Tognon, Karin D. Rodland
Proteogenomics refers to the integration of comprehensive genomic, transcriptomic, and proteomic measurements from the same samples with the goal of fully understanding the regulatory processes converting genotypes to phenotypes, often with an emphasis on gaining a deeper understanding of disease processes. Although specific genetic mutations have long been known to drive the development of multiple
-
Circadian Regulation of Drug Responses: Toward Sex-Specific and Personalized Chronotherapy Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-19 Francis A. Lévi, Alper Okyar, Eva Hadadi, Pasquale F. Innominato, Annabelle Ballesta
Today's challenge for precision medicine involves the integration of the impact of molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements of tolerability and/or efficacy of medications through proper administration timing have been confirmed over the past decade for immunotherapy and chemotherapy against cancer, as well as for commonly
-
Novel Immunopharmacological Drugs for the Treatment of Allergic Diseases Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-19 Ekaterini Tiligada, Daria Gafarov, Maria Zaimi, Joana Vitte, Francesca Levi-Schaffer
The exponential rise in the prevalence of allergic diseases since the mid-twentieth century has led to a genuine public health emergency and has also fostered major progress in research on the underlying mechanisms and potential treatments. The management of allergic diseases benefits from the biological revolution, with an array of novel immunomodulatory therapeutic and investigational tools targeting
-
Deciphering Drug Targets and Actions with Single-Cell and Spatial Resolution Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-19 Zhengyuan Pang, Benjamin F. Cravatt, Li Ye
Recent advances in chemical, molecular, and genetic approaches have provided us with an unprecedented capacity to identify drug-target interactions across the whole proteome and genome. Meanwhile, rapid developments of single-cell and spatial omics technologies are revolutionizing our understanding of the molecular architecture of biological systems. However, a significant gap remains in how we align
-
Translational In Vivo Assays in Behavioral Biology Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-14 Sarah L. Withey, Diego A. Pizzagalli, Jack Bergman
The failure of preclinical research to advance successful candidate medications in psychiatry has created a paradigmatic crisis in psychiatry. The Research Domain Criteria (RDoC) initiative was designed to remedy this situation with a neuroscience-based approach that employs multimodal and cross-species in vivo methodology to increase the probability of translational findings and, consequently, drug
-
Molecular Activation of NLRP3 Inflammasome by Particles and Crystals: A Continuing Challenge of Immunology and Toxicology Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-14 Qiang Ma, Chol Seung Lim
Particles and crystals constitute a unique class of toxic agents that humans are constantly exposed to both endogenously and from the environment. Deposition of particulates in the body is associated with a range of diseases and toxicity. The mechanism by which particulates cause disease remains poorly understood due to the lack of mechanistic insights into particle-biological interactions. Recent
-
Orexin Receptor Antagonism: Normalizing Sleep Architecture in Old Age and Disease Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-14 Jarrah O.-Z.J. Kron, Ryan J. Keenan, Daniel Hoyer, Laura H. Jacobson
Sleep is essential for human well-being, yet the quality and quantity of sleep reduce as age advances. Older persons (>65 years old) are more at risk of disorders accompanied and/or exacerbated by poor sleep. Furthermore, evidence supports a bidirectional relationship between disrupted sleep and Alzheimer's disease (AD) or related dementias. Orexin/hypocretin neuropeptides stabilize wakefulness, and
-
G Protein–Coupled Receptor Signaling: New Insights Define Cellular Nanodomains Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-09-08 Martin J. Lohse, Andreas Bock, Manuela Zaccolo
G protein–coupled receptors are the largest and pharmacologically most important receptor family and are involved in the regulation of most cell functions. Most of them reside exclusively at the cell surface, from where they signal via heterotrimeric G proteins to control the production of second messengers such as cAMP and IP3 as well as the activity of several ion channels. However, they may also
-
Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-16 Roman Tremmel, Ute Hofmann, Mathias Haag, Elke Schaeffeler, Matthias Schwab
Pharmacogenomics (PGx) enables personalized treatment for the prediction of drug response and to avoid adverse drug reactions. Currently, PGx mainly relies on the genetic information of absorption, distribution, metabolism, and excretion (ADME) targets such as drug-metabolizing enzymes or transporters to predict differences in the patient's phenotype. However, there is evidence that the phenotype-genotype
-
Targeting Efferocytosis in Inflammaging Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-16 Ivan K.H. Poon, Kodi S. Ravichandran
Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized
-
From Thalidomide to Rational Molecular Glue Design for Targeted Protein Degradation Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-16 Vladas Oleinikovas, Pablo Gainza, Thomas Ryckmans, Bernhard Fasching, Nicolas H. Thomä
Thalidomide and its derivatives are powerful cancer therapeutics that are among the best-understood molecular glue degraders (MGDs). These drugs selectively reprogram the E3 ubiquitin ligase cereblon (CRBN) to commit target proteins for degradation by the ubiquitin-proteasome system. MGDs create novel recognition interfaces on the surface of the E3 ligase that engage in induced protein-protein interactions
-
Apathy and Motivation: Biological Basis and Drug Treatment Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-16 Harry Costello, Masud Husain, Jonathan P. Roiser
Apathy is a disabling syndrome associated with poor functional outcomes that is common across a broad range of neurological and psychiatric conditions. Currently, there are no established therapies specifically for the condition, and safe and effective treatments are urgently needed. Advances in the understanding of motivation and goal-directed behavior in humans and animals have shed light on the
-
The Nocebo Effect Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-16 Luana Colloca
Adverse nocebo responses can cause harm to patients and interfere with treatment adherence and effects in both clinic practice and clinical trials. Nocebo responses refer to negative outcomes to active medical treatments in clinical trials or practice that cannot be explained by the treatment's pharmacologic effects. Negative expectancies and nocebo effects are less known than placebo responses. Nocebo
-
Health Digital Twins in Life Science and Health Care Innovation Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-10 Kaushik P. Venkatesh, Gabriel Brito, Maged N. Kamel Boulos
Health digital twins (HDTs) are virtual representations of real individuals that can be used to simulate human physiology, disease, and drug effects. HDTs can be used to improve drug discovery and development by providing a data-driven approach to inform target selection, drug delivery, and design of clinical trials. HDTs also offer new applications into precision therapies and clinical decision making
-
Hear and Now: Ongoing Clinical Trials to Prevent Drug-Induced Hearing Loss Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-10 John Lee, Katharine Fernandez, Lisa L. Cunningham
Each year over half a million people experience permanent hearing loss caused by treatment with therapeutic drugs with ototoxic side effects. There is a major unmet clinical need for therapies that protect against this hearing loss without reducing the therapeutic efficacy of these lifesaving drugs. At least 17 clinical trials evaluating 10 therapeutics are currently underway for therapies aimed at
-
Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-08 Eric J. Nunes, Nii A. Addy, P. Jeffrey Conn, Daniel J. Foster
Cholinergic regulation of dopamine (DA) signaling has significant implications for numerous disorders, including schizophrenia, substance use disorders, and mood-related disorders. The activity of midbrain DA neurons and DA release patterns in terminal regions are tightly regulated by cholinergic neurons found in both the striatum and the hindbrain. These cholinergic neurons can modulate DA circuitry
-
Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-08-01 Ruth Nussinov, Hyunbum Jang
Here we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load
-
LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-07-28 Erfan Tasdighi, Rishav Adhikari, Omar Almaadawy, Thorsten M. Leucker, Michael J. Blaha
Lipoprotein(a) [Lp(a)] is a molecule bound to apolipoprotein(a) with some similarity to low-density lipoprotein cholesterol (LDL-C), which has been found to be a risk factor for cardiovascular disease (CVD). Lp(a) appears to induce inflammation, atherogenesis, and thrombosis. Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics. Current clinical
-
High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-07-28 Caitlin Lynch, Srilatha Sakamuru, Masato Ooka, Ruili Huang, Carleen Klumpp-Thomas, Paul Shinn, David Gerhold, Anna Rossoshek, Sam Michael, Warren Casey, Michael F. Santillo, Suzanne Fitzpatrick, Russell S. Thomas, Anton Simeonov, Menghang Xia
Traditionally, chemical toxicity is determined by in vivo animal studies, which are low throughput, expensive, and sometimes fail to predict compound toxicity in humans. Due to the increasing number of chemicals in use and the high rate of drug candidate failure due to toxicity, it is imperative to develop in vitro, high-throughput screening methods to determine toxicity. The Tox21 program, a unique
-
Pharmacogenomics Beyond Single Common Genetic Variants: The Way Forward Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-07-28 Volker M. Lauschke, Yitian Zhou, Magnus Ingelman-Sundberg
Interindividual variability in genes encoding drug-metabolizing enzymes, transporters, receptors, and human leukocyte antigens has a major impact on a patient's response to drugs with regard to efficacy and safety. Enabled by both technological and conceptual advances, the field of pharmacogenomics is developing rapidly. Major progress in omics profiling methods has enabled novel genotypic and phenotypic
-
Pros and Cons of Long-Chain Omega-3 Polyunsaturated Fatty Acids in Cardiovascular Health Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-01-20 Ivana Djuricic, Philip C. Calder
The long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in seafood, supplements, and concentrated pharmaceutical preparations. Prospective cohort studies demonstrate an association between higher intakes of EPA+DHA or higher levels of EPA and DHA in the body and lower risk of developing cardiovascular disease (CVD), especially coronary heart disease
-
Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable? Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-01-20 Shanelle R. Shillingford, Anton M. Bennett
Phosphatases and kinases maintain an equilibrium of dephosphorylated and phosphorylated proteins, respectively, that are required for critical cellular functions. Imbalance in this equilibrium or irregularity in their function causes unfavorable cellular effects that have been implicated in the development of numerous diseases. Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of
-
Lipoxin Mimetics and the Resolution of Inflammation Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-01-20 Catherine Godson, Patrick Guiry, Eoin Brennan
Inflammation and its timely resolution are critical to ensure effective host defense and appropriate tissue repair after injury and or infection. Chronic, unresolved inflammation typifies many prevalent pathologies. The key mediators that initiate and drive the inflammatory response are well defined and targeted by conventional anti-inflammatory therapeutics. More recently, there is a growing appreciation
-
G Protein–Coupled Estrogen Receptor GPER: Molecular Pharmacology and Therapeutic Applications Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-01-20 Jeffrey B. Arterburn, Eric R. Prossnitz
The actions of estrogens and related estrogenic molecules are complex and multifaceted in both sexes. A wide array of natural, synthetic, and therapeutic molecules target pathways that produce and respond to estrogens. Multiple receptors promulgate these responses, including the classical estrogen receptors of the nuclear hormone receptor family (estrogen receptors α and β), which function largely
-
Roadmap for Achieving Universal Antiretroviral Treatment Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-01-20 Simiso Sokhela, Samanta Lalla-Edward, Mark J. Siedner, Mohammed Majam, Willem Daniel Francois Venter
Modern antiretroviral therapy safely, potently, and durably suppresses human immunodeficiency virus (HIV) that, if left untreated, predictably causes acquired immunodeficiency syndrome (AIDS), which has been responsible for tens of millions of deaths globally since it was described in 1981. In one of the most extraordinary medical success stories in modern times, a combination of pioneering basic science
-
Neuropathic Pain: Mechanisms, Sex Differences, and Potential Therapies for a Global Problem Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-01-20 Shahrzad Ghazisaeidi, Milind M. Muley, Michael W. Salter
The study of chronic pain continues to generate ever-increasing numbers of publications, but safe and efficacious treatments for chronic pain remain elusive. Recognition of sex-specific mechanisms underlying chronic pain has resulted in a surge of studies that include both sexes. A predominant focus has been on identifying sex differences, yet many newly identified cellular mechanisms and alterations
-
Harnessing the Power of Electronic Health Records and Genomics for Drug Discovery Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2023-01-20 Kristi Krebs, Lili Milani
A long-standing recognition that information from human genetics studies has the potential to accelerate drug discovery has led to decades of research on how to leverage genetic and phenotypic information for drug discovery. Established simple and advanced statistical methods that allow the simultaneous analysis of genotype and clinical phenotype data by genome- and phenome-wide analyses, colocalization
-
Introduction to the Theme “Development of New Drugs: Moving from the Bench to Bedside and Improved Patient Care” Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-10-21 Terrence F. Blaschke, Paul A. Insel, Susan G. Amara, Urs A. Meyer
Investigations in pharmacology and toxicology range from molecular studies to clinical care. Studies in basic and clinical pharmacology and in preclinical and clinical toxicology are all essential in bringing new knowledge and new drugs into clinical use. The 30 reviews in Volume 63 of the Annual Review of Pharmacology and Toxicology explore topics across this spectrum. Examples include “Zebrafish
-
OAT, OATP, and MRP Drug Transporters and the Remote Sensing and Signaling Theory Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-10-07 Sanjay K. Nigam, Jeffry C. Granados
The coordinated movement of organic anions (e.g., drugs, metabolites, signaling molecules, nutrients, antioxidants, gut microbiome products) between tissues and body fluids depends, in large part, on organic anion transporters (OATs) [solute carrier 22 (SLC22)], organic anion transporting polypeptides (OATPs) [solute carrier organic (SLCO)], and multidrug resistance proteins (MRPs) [ATP-binding cassette
-
Beyond Erectile Dysfunction: cGMP-Specific Phosphodiesterase 5 Inhibitors for Other Clinical Disorders Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-10-07 Arun Samidurai, Lei Xi, Anindita Das, Rakesh C. Kukreja
Cyclic guanosine monophosphate (cGMP), an important intracellular second messenger, mediates cellular functional responses in all vital organs. Phosphodiesterase 5 (PDE5) is one of the 11 members of the cyclic nucleotide phosphodiesterase (PDE) family that specifically targets cGMP generated by nitric oxide–driven activation of the soluble guanylyl cyclase. PDE5 inhibitors, including sildenafil and
-
An Aspirin a Day: New Pharmacological Developments and Cancer Chemoprevention Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-10-06 David G. Menter, Robert S. Bresalier
Chemoprevention refers to the use of natural or synthetic agents to reverse, suppress, or prevent the progression or recurrence of cancer. A large body of preclinical and clinical data suggest the ability of aspirin to prevent precursor lesions and cancers, but much of the clinical data are inferential and based on descriptive epidemiology, case control, and cohort studies or studies designed to answer
-
Understanding the Chemical Exposome During Fetal Development and Early Childhood: A Review Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-10-06 Magdaléna Krausová, Dominik Braun, Tina Buerki-Thurnherr, Claudia Gundacker, Eva Schernhammer, Lukas Wisgrill, Benedikt Warth
Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism
-
Personalized Therapeutics for KATP-Dependent Pathologies Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-28 Colin G. Nichols
Ubiquitously expressed throughout the body, ATP-sensitive potassium (KATP) channels couple cellular metabolism to electrical activity in multiple tissues; their unique assembly as four Kir6 pore-forming subunits and four sulfonylurea receptor (SUR) subunits has resulted in a large armory of selective channel opener and inhibitor drugs. The spectrum of monogenic pathologies that result from gain- or
-
Biased Agonism: Lessons from Studies of Opioid Receptor Agonists Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-28 Eamonn Kelly, Alexandra Conibear, Graeme Henderson
In ligand bias different agonist drugs are thought to produce distinct signaling outputs when activating the same receptor. If these signaling outputs mediate therapeutic versus adverse drug effects, then agonists that selectively activate the therapeutic signaling pathway would be extremely beneficial. It has long been thought that μ-opioid receptor agonists that selectively activate G protein– over
-
Pharmacological Interventions in Labor and Delivery Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-24 Susan Wray, Sarah Arrowsmith, Andrew Sharp
While there is not a wide range of pregnancy-specific drugs, there are some very specific high-risk areas of obstetric care for which unique pharmacological approaches have been established. In preterm birth, labor induction and augmentation, and the management of postpartum hemorrhage, these pharmacological approaches have become the bedrock in managing some of the most common and problematic areas
-
Resolution Pharmacology: Focus on Pro-Resolving Annexin A1 and Lipid Mediators for Therapeutic Innovation in Inflammation Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-24 Mauro Perretti, Jesmond Dalli
Chronic diseases that affect our society are made more complex by comorbidities and are poorly managed by the current pharmacology. While all present inflammatory etiopathogeneses, there is an unmet need for better clinical management of these diseases and their multiple symptoms. We discuss here an innovative approach based on the biology of the resolution of inflammation. Studying endogenous pro-resolving
-
Cognitive Impairment Associated with Schizophrenia: From Pathophysiology to Treatment Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-24 Daniel C. Javitt
Cognitive impairment is a core feature of schizophrenia and a major contributor to poor functional outcomes. Methods for assessment of cognitive dysfunction in schizophrenia are now well established. In addition, there has been increasing appreciation in recent years of the additional role of social cognitive impairment in driving functional outcomes and of the contributions of sensory-level dysfunction
-
Zebrafish as a Mainstream Model for In Vivo Systems Pharmacology and Toxicology Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-24 Calum A. MacRae, Randall T. Peterson
Pharmacology and toxicology are part of a much broader effort to understand the relationship between chemistry and biology. While biomedicine has necessarily focused on specific cases, typically of direct human relevance, there are real advantages in pursuing more systematic approaches to characterizing how health and disease are influenced by small molecules and other interventions. In this context
-
Lysosomal Ion Channels: What Are They Good For and Are They Druggable Targets? Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-24 Erika Riederer, Chunlei Cang, Dejian Ren
Lysosomes play fundamental roles in material digestion, cellular clearance, recycling, exocytosis, wound repair, Ca2+ signaling, nutrient signaling, and gene expression regulation. The organelle also serves as a hub for important signaling networks involving the mTOR and AKT kinases. Electrophysiological recording and molecular and structural studies in the past decade have uncovered several unique
-
Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-21 Jesper Z. Haeggström, Marcia E. Newcomer
Leukotrienes are potent immune-regulating lipid mediators with patho-genic roles in inflammatory and allergic diseases, particularly asthma. These autacoids also contribute to low-grade inflammation, a hallmark of cardiovascular, neurodegenerative, metabolic, and tumor diseases. Biosynthesis of leukotrienes involves release and oxidative metabolism of arachidonic acid and proceeds via a set of cytosolic
-
The Duality of Arsenic Metabolism: Impact on Human Health Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-13 Mahmoud A. El-Ghiaty, Ayman O.S. El-Kadi
Arsenic is a naturally occurring hazardous element that is environmentally ubiquitous in various chemical forms. Upon exposure, the human body initiates an elimination pathway of progressive methylation into relatively less bioreactive and more easily excretable pentavalent methylated forms. Given its association with decreasing the internal burden of arsenic with ensuing attenuation of its related
-
Specialized Pro-Resolving Mediators as Resolution Pharmacology for the Control of Pain and Itch Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-13 Ru-Rong Ji
Specialized pro-resolving mediators (SPMs), including resolvins, protectins, and maresins, are endogenous lipid mediators that are synthesized from omega-3 polyunsaturated fatty acids during the acute phase or resolution phase of inflammation. Synthetic SPMs possess broad safety profiles and exhibit potent actions in resolving inflammation in preclinical models. Accumulating evidence in the past decade
-
Fibroblast Growth Factor–Based Pharmacotherapies for the Treatment of Obesity-Related Metabolic Complications Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-13 Leigang Jin, Ranyao Yang, Leiluo Geng, Aimin Xu
The fibroblast growth factor (FGF) family, which comprises 22 structurally related proteins, plays diverse roles in cell proliferation, differentiation, development, and metabolism. Among them, two classical members (FGF1 and FGF4) and two endocrine members (FGF19 and FGF21) are important regulators of whole-body energy homeostasis, glucose/lipid metabolism, and insulin sensitivity. Preclinical studies
-
Age-Related Perioperative Neurocognitive Disorders: Experimental Models and Druggable Targets Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-09-13 Odmara L. Barreto Chang, Katherine L. Possin, Mervyn Maze
With the worldwide increase in life span, surgical patients are becoming older and have a greater propensity for postoperative cognitive impairment, either new onset or through deterioration of an existing condition; in both conditions, knowledge of the patient's preoperative cognitive function and postoperative cognitive trajectory is imperative. We describe the clinical utility of a tablet-based
-
Air Pollution–Related Neurotoxicity Across the Life Span Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-08-27 Deborah A. Cory-Slechta, Alyssa Merrill, Marissa Sobolewski
Air pollution is a complex mixture of gases and particulate matter, with adsorbed organic and inorganic contaminants, to which exposure is lifelong. Epidemiological studies increasingly associate air pollution with multiple neurodevelopmental disorders and neurodegenerative diseases, findings supported by experimental animal models. This breadth of neurotoxicity across these central nervous system
-
Pharmacological Induction of Granulocyte Cell Death as Therapeutic Strategy Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-08-27 Thomas Kaufmann, Hans-Uwe Simon
Apoptosis is central for the maintenance of health. In the immune system, apoptosis guarantees proper development of immune cells and shutdown of immune reactions by the coordinated elimination of activated immune cells. Limitation of the life span of granulocytes is important, as overactivation of these cells is associated with chronic inflammation and collateral tissue damage. Consequently, targeted
-
CaMKII as a Therapeutic Target in Cardiovascular Disease Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-08-17 Oscar E. Reyes Gaido, Lubika J. Nkashama, Kate L. Schole, Qinchuan Wang, Priya Umapathi, Olurotimi O. Mesubi, Klitos Konstantinidis, Elizabeth D. Luczak, Mark E. Anderson
CaMKII (the multifunctional Ca2+ and calmodulin-dependent protein kinase II) is a highly validated signal for promoting a variety of common diseases, particularly in the cardiovascular system. Despite substantial amounts of convincing preclinical data, CaMKII inhibitors have yet to emerge in clinical practice. Therapeutic inhibition is challenged by the diversity of CaMKII isoforms and splice variants
-
Pharmacogenetics of Antiplatelet Therapy Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-08-01 Matteo Castrichini, Jasmine A. Luzum, Naveen Pereira
Antiplatelet therapy is used in the treatment of patients with acute coronary syndromes, stroke, and those undergoing percutaneous coronary intervention. Clopidogrel is the most widely used antiplatelet P2Y12 inhibitor in clinical practice. Genetic variation in CYP2C19 may influence its enzymatic activity, resulting in individuals who are carriers of loss-of-function CYP2C19 alleles and thus have reduced
-
Synthetic Cannabinoids: A Pharmacological and Toxicological Overview Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-08-01 Rita Roque-Bravo, Rafaela Sofia Silva, Rui F. Malheiro, Helena Carmo, Félix Carvalho, Diana Dias da Silva, João Pedro Silva
Synthetic cannabinoids (SCs) are a chemically diverse group of new psychoactive substances (NPSs) that target the endocannabinoid system, triggering a plethora of actions (e.g., elevated mood sensation, relaxation, appetite stimulation) that resemble, but are more intense than, those induced by cannabis. Although some of these effects have been explored for therapeutic applications, anticipated stronger
-
A Delightful Trip Along the Pathway of Cannabinoid and Endocannabinoid Chemistry and Pharmacology Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-07-18 Raphael Mechoulam
After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the last few decades, most of my research has been on plant cannabinoids, the endogenous cannabinoids arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl
-
Artificial Intelligence and Machine Learning for Lead-to-Candidate Decision-Making and Beyond Annu. Rev. Pharmacol. Toxicol. (IF 12.5) Pub Date : 2022-06-09 Douglas McNair
The use of artificial intelligence (AI) and machine learning (ML) in pharmaceutical research and development has to date focused on research: target identification; docking-, fragment-, and motif-based generation of compound libraries; modeling of synthesis feasibility; rank-ordering likely hits according to structural and chemometric similarity to compounds having known activity and affinity to the