Annual Review of Pharmacology and Toxicology药理学与毒理学年度综述
Annual Review of Pharmacology and Toxicology(英文缩写 ANNU REV PHARMACOL),ISSN 0362-1642,eISSN 1545-4304,中文译名:药理学与毒理学年度综述 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 16.459 | Q1 |
| 2022 | 12.500 | Q1 |
| 2023 | 11.200 | Q1 |
| 2024 | 13.100 | Q1 |
| 2025 | 19.000 | Q1 |
Annual Review of Pharmacology and Toxicology 最新收录文献
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1. Molecular Pharmacology of Dopamine Receptors: Structure, Function, and Therapeutic Implications.
PMID:日期:2026-10-01Dopamine receptors (DRs) mediate central and peripheral dopaminergic signaling and remain major therapeutic targets in movement disorders, psychiatric disease, and endocrine dysfunction. Despite decades of clinical use, existing DR-directed therapies still suffer from limited subtype selectivity, pathway-nonspecific engagement, and substantial adverse effects, reflecting an incomplete molecular understanding of receptor function. In this review, we examine recent advances in DR molecular pharmacology, focusing on how structural, pharmacological, and computational studies have clarified receptor activation, inverse agonism, transducer coupling, signaling bias, allosteric modulation, and ligand selectivity through analyses of inactive and active receptor states, including family-wide receptor-G protein complexes. We discuss how ligand-specific receptor conformations, transducer interactions, and membrane environment shape signaling output, help explain the diverse actions of dopaminergic ligands, and distinguish the activation trajectories of D1-like and D2-like receptors. We also consider how these advances, including insights into allosteric sites, transducer selectivity, and AI-assisted discovery, inform the development of more selective and precise dopaminergic therapies. Together, these developments are shifting the field from descriptive receptor pharmacology toward a mechanistic and structure-guided framework for therapeutic discovery.
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2. Emerging Roles of Mass Spectrometry-Based Proteomics in Drug Discovery.
PMID:日期:2026-10-01Mass spectrometry (MS)-based proteomics has emerged as a versatile platform in modern drug discovery, enabling system-wide interrogation of protein abundance, posttranslational modifications (PTMs), turnover, structural stability, and interactions with small molecules in native biological contexts. In this review, we introduce recent advances in MS and summarize how scalable, high-throughput technologies support target identification and mechanism-of-action studies. We discuss global profiling of the proteome and PTMs under drug perturbation, as well as proteome-wide stability assays such as thermal proteome profiling and limited proteolysis-MS. We further discuss activity-based protein profiling, fully functionalized and photoaffinity probes, and affinity-matrix approaches that expand covalent and noncovalent ligand discovery. Finally, we highlight multiple proteomics-driven strategies in targeted protein degradation. Together, these integrated MS-based approaches in drug discovery, often termed chemoproteomics, provide a coherent framework for linking chemical perturbations to functional proteome remodeling, expanding the druggable proteome and accelerating therapeutic development.
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3. {"_":"Novel Targets and Treatments for Neurodegenerative Diseases Revealed by .","i":["Drosophila"]}
PMID:日期:2026-09-25Neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson's disease, and others lack any disease-modifying therapy due to the lack of mechanistic understanding of the disease etiology. The genetic tractability, short lifespan, and conserved cellular biology of have positioned the fly as a powerful model organism for a pathway-driven therapeutic discovery across NDDs. Fly models expressing human pathogenic proteins, including Aβ, tau, α-synuclein, and others, recapitulate core features of these NDDs such as proteostasis defects, RNA dysregulation, mitochondrial dysfunction, lipid signaling abnormalities, and innate immune activation. Unbiased genetic and pharmacologic screens in these systems have identified conserved therapeutic nodes such as PARP signaling and insulin/IGF pathways. In this review, we discuss these advances to define conserved therapeutic axes identified in and evaluate their translational potential for neurodegenerative disorders.
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4. Use of High-Resolution Mass Spectrometry in Therapeutic Drug Monitoring of Psychiatric Drugs.
PMID:日期:2026-09-17Psychiatric diseases are among the most challenging health issues in terms of human suffering, complex treatments, frequent treatment failure, high degrees of disability and sick leave usage, and high social expenditure. For many patients, chronic drug treatment is often required. However, many patients experience insufficient clinical effects or side effects. Therapeutic drug monitoring (TDM) of plasma/serum concentration of psychiatric drugs aims to facilitate precision dosing and improve outcomes. High-resolution mass spectrometry (HR-MS) is a powerful technique to refine TDM with excellent specificity and sensitivity by measuring the exact mass of drugs and metabolites. The benefits of such an analytical method include that many compounds can be measured simultaneously and with short run times. Additional applications include retrospective data reprocessing to reveal interacting comedications, active/toxic metabolites, and dosing biomarkers, in which researchers reprocess exact masses of stored HR-MS TDM files. This review illustrates the benefits of HR-MS-based TDM focusing on psychiatry and innovative applications.
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5. New Natural Product Antibiotics: Strategies and Tools That Offer New Approaches to Overcome Traditional Roadblocks.
PMID:日期:2026-08-27Microbial natural products have been the cornerstone of antibiotics used in medicine since their discovery in the early twentieth century. Shaped by natural selection, natural products are privileged compounds that often target complex biological systems. Despite this success, they have increasingly been abandoned by the drug discovery industry. A principal reason for moving away from natural products is the repeated identification of common antibiotic chemical scaffolds through traditional cell-killing phenotypic assays. However, synthetic compounds have largely failed to fill the antibiotic discovery gap. Advances in genomics, bioinformatics, and analytical chemistry have, in recent years, combined to show that there is still significant chemical diversity to be explored in microbes, providing an opportunity to revisit natural products for antibiotic discovery. Sourcing compounds from rare organisms through genome mining and rapid triage using metabolomics are being used to find new compounds with novel modes of action, opening the door to a new era in antibiotic innovation.
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6. Making Drug Dosing Decisions Based on Therapeutic Monitoring.
PMID:日期:2026-08-14We review a new methodology for deriving pharmacokinetic clearance equations independent of differential equations or mechanistic models of drug disposition. Nine examples are presented that illustrate the application of this framework to drug dosing decisions based on therapeutic monitoring. Although mass balance is necessary and sufficient in deriving in vitro measures and rate constants relevant to in vivo pharmacokinetics, clinical drug dosing decisions are based on clearance, not rate constants. Mass balance is necessary in deriving pharmacokinetic clearance equations, but in vivo it is not always sufficient in determining which processes drive overall clearance. A key implication of this framework is that pharmaceutical sponsors may possibly formulate a dosage form for high-clearance drugs, where the manufactured delivery clearance from the dosage form becomes the in vivo clearance of drug in the patient, independent of the elimination clearance observed following an intravenous bolus dose and independent of the patient-specific characteristics.
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7. Pharmacoexposomics: The Environmental Complement to Pharmacogenomics to Advance Precision Medicine.
PMID:日期:2026-08-13Despite advances in pharmacogenomics that have led to innovative therapeutic strategies, substantial interindividual variability in drug efficacy and toxicity persists. Both endogenous and exogenous factors contribute to this unexplained variation, resulting in suboptimal treatment effectiveness, unnecessary healthcare costs, preventable mortality, and significant human suffering. The emerging field of exposomics is aimed at addressing the complex exposures that impact human health and offers an opportunity to interrogate how these exposures influence drug actions and outcomes. Here, we introduce pharmacoexposomics as a complementary framework that systematically quantifies the body's metabolic response to drug and environmental exposures using high-resolution mass spectrometry. We then present IndiPHARM (Individualized Pharmacology), a multi-institution, Advanced Research Projects Agency for Health-supported platform designed to integrate population-scale pharmacoexposomics with pharmacogenomics and clinical data to elucidate interindividual variability in drug response, identify adverse reactions, and inform tailored, effective treatment strategies that advance precision medicine.
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8. {"_":"Nonaddictive Analgesia: New Approaches That Target the Hodgkin-Huxley Na/K Dyad.","sub":["V","V"]}
PMID:日期:2026-08-13Chronic pain represents a massive global health burden that is exacerbated by the limitations and liabilities of opioid therapies. This review examines the biophysical basis of nociceptor excitability, framed by the Hodgkin-Huxley dyad of opposing voltage-gated sodium (Na) and potassium (K) conductances. We analyze the roles of peripheral Na isoforms (Na1.7, Na1.8, Na1.9) as drivers of pathological firing and discuss the translational trajectory of Na inhibitors, ranging from the recent clinical approval of Na1.8-selective small molecules to the ongoing challenges facing Na1.7-targeted programs. Beyond canonical pore blockers, we evaluate emerging modalities, including state-dependent cannabinoid modulation, targeted protein degradation, and genetic interventions. Complementing these excitatory targets, we discuss K7 channel activators as molecular brakes capable of buffering hyperexcitability. Finally, we propose that rational comodulation of this dyad offers a mechanistically grounded pathway toward effective, nonaddictive analgesia.
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9. Beyond Catalytic Inhibition: The Evolving Landscape of PARP Pharmacology.
PMID:日期:2026-08-10Since the identification of PARP1/2 as synthetic lethal targets in BRCA-deficient breast cancer and the subsequent approval of catalytic domain-targeting PARP inhibitors, the landscape of PARP inhibitors has expanded to encompass a broader chemical tool kit. Beyond PARP1/2's canonical role in DNA repair, PARP inhibitors have revealed context-dependent PARP functions in anticancer immunity, viral infection, neurodegeneration, and cellular organization. These discoveries have motivated new strategies that extend past targeting catalytic domains. In this review, we highlight three emerging directions: () biological insights revealed by PARP1/2 inhibitors in oncology and other settings, () progress in developing inhibitors against PARP family members beyond PARP1/2, and () approaches that target noncatalytic domains or modulate PARP function through mechanisms such as interface disruption and targeted degradation. We conclude by outlining key next steps for advancing PARP pharmacology, including substrate mapping, utilizing rational polypharmacology, targeting ADP-ribose readers and erasers, and expanding structural coverage of PARP family proteins.
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10. Vesicular Monoamine Transporters at the Crossroads of Structure and Function: Advances, Challenges, and Future Perspectives.
PMID:日期:2026-08-07Monoaminergic signaling controls many aspects of human physiology, including autonomic responses, movement, and emotion. The vesicular monoamine transporters (VMAT1 and VMAT2) sequester monoamines into synaptic vesicles within the central and peripheral nervous system. Dysregulation of VMAT function contributes to neuropsychiatric and neurodegenerative disorders, including Parkinson's disease, depression, and psychostimulant substance abuse. Clinically, VMATs are targeted by the inhibitors tetrabenazine and reserpine, used to treat hyperkinetic movement disorders and hypertension, respectively, while amphetamines exploit VMAT2-mediated dopamine efflux to treat ADHD. Emerging VMAT2-selective compounds such as lobeline derivatives and GZ-11610 attenuate psychostimulant reinforcement. Tricyclic antidepressants upregulate VMAT2 function and rescue disease-causing variants, highlighting VMAT2 as a promising therapeutic target. Despite their importance, the molecular mechanisms driving proton-coupled transport, inhibition, and psychostimulant action remain poorly understood. This review summarizes current biochemical, structural, and functional insights into VMATs, highlighting proton coupling, transport kinetics, inhibition mechanisms, unresolved questions, and future research directions.