自 1961 年出版的《药理学和毒理学年度评论》涵盖了药理学和毒理学领域的重大发展，包括受体、转运蛋白、酶和化学试剂；药物开发科学；免疫系统、中枢和自主神经系统、胃肠系统、心血管系统、内分泌系统和肺系统等系统；和专题。

The Annual Review of Pharmacology and Toxicology, published since 1961, covers significant developments in the fields of pharmacology and toxicology, including research on receptors, transport proteins, enzymes, and chemical agents; the science of drug development; and topics related to various systems such as the immune system, central and autonomic nervous systems, gastrointestinal system, cardiovascular system, endocrine system, and pulmonary system.

《Annual Review of Pharmacology and Toxicology》自1961年出版，涵盖了药理学和毒理学领域的重要进展，包括受体、转运蛋白、酶和化学试剂的研究；药物开发的科学；以及免疫系统、中枢神经系统、自主神经系统、胃肠系统、心血管系统、内分泌系统和肺系统等多个系统的相关内容。

Annual Review of Pharmacology and Toxicology

▪ Abstract The neonicotinoids, the newest major class of insecticides, have outstanding potency and systemic action for crop protection against piercing-sucking pests, and they are highly effective for flea control on cats and dogs. Their common names are acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam. They generally have low toxicity to mammals (acute and chronic), birds, and fish. Biotransformations involve some activation reactions but largely detoxification mechanisms. In contrast to nicotine, epibatidine, and other ammonium or iminium nicotinoids, which are mostly protonated at physiological pH, the neonicotinoids are not protonated and have an electronegative nitro or cyano pharmacophore. Agonist recognition by the nicotinic receptor involves cation-π interaction for nicotinoids in mammals and possibly a cationic subsite for interaction with the nitro or cyano substituent of neonicotinoids in insects. The low affinity of neonicotinoids for vertebrate relative to insect nicotinic receptors is a major factor in their favorable toxicological profile.

Motohiro Tomizawa

John E. Casida

The Annual Review of Pharmacology and Toxicology

Annu. Rev. Pharmacol. Toxicol.

NEONICOTINOID INSECTICIDE TOXICOLOGY: Mechanisms of Selective Action

新烟碱类杀虫剂毒理学：选择性作用机制

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 technique for rapid assessment of the memory and attentiveness domains required for executive function. The pathogenic mechanisms for perioperative neurocognitive disorders have been investigated in animal models in which excessive and/or prolonged postoperative neuroinflammation has emerged as a likely contender. The cellular and molecular species involved in postoperative neuroinflammation are the putative targets for future therapeutic interventions that are efficacious and do not interfere with the surgical patient's healing process.

Odmara L. Barreto Chang

Katherine L. Possin

Mervyn Maze

Age-Related Perioperative Neurocognitive Disorders: Experimental Models and Druggable Targets

围手术期神经认知障碍的年龄相关性：实验模型与可药物靶点

Tinnitus is a highly prevalent condition that is associated with hearing loss in most cases. In the absence of external stimuli, phantom perceptions of sounds emerge from alterations in neuronal activity within central auditory and nonauditory structures. Pioneering studies using lidocaine revealed that tinnitus is susceptible to pharmacological interventions. However, lidocaine is not effective in all patients, and no other drug has been identified with clear efficacy for the long-term treatment of tinnitus. In this review, we present recent advances in tinnitus research, including more detailed knowledge of its pathophysiology and involved neurotransmitter systems. Moreover, we summarize results from animal and clinical treatment studies as well as from studies that identified tinnitus as a side effect of pharmacological treatments. Finally, we focus on challenges in the development of pharmacological compounds for the treatment of tinnitus, namely the limitations of available animal models and of standardized clinical research methodologies.

Berthold Langguth

Ana Belen Elgoyhen

Christopher R. Cederroth

Therapeutic Approaches to the Treatment of Tinnitus

耳鸣治疗的疗法

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 lysosomal ion channels and transporters, including TPCs, TMEM175, TRPMLs, CLN7, and CLC-7. They underlie the organelle's permeability to major ions, including K+, Na+, H+, Ca2+, and Cl-. The channels are regulated by numerous cellular factors, ranging from H+ in the lumen and voltage across the lysosomal membrane to ATP in the cytosol to growth factors outside the cell. Genetic variations in the channel/transporter genes are associated with diseases that include lysosomal storage diseases and neurodegenerative diseases. Recent studies with human genetics and channel activators suggest that lysosomal channels may be attractive targets for the development of therapeutics for the prevention of and intervention in human diseases.

Erika Riederer

Chunlei Cang

Dejian Ren

Lysosomal Ion Channels: What Are They Good For and Are They Druggable Targets?

溶酶体离子通道：它们有什么用处，是否可作为药物靶点？

The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that participate in the modulation of synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signaling partners. A great deal of progress has been made in determining the mechanisms by which mGluRs are activated, proteins with which they interact, and orthosteric and allosteric ligands that can modulate receptor activity. The widespread expression of mGluRs makes these receptors particularly attractive drug targets, and recent studies continue to validate the therapeutic utility of mGluR ligands in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia.

Colleen M. Niswender

P. Jeffrey Conn

Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease

代谢型谷氨酸受体：生理学、药理学与疾病

Advances in molecular biology and molecular genetics as well as major scientific breakthroughs in immunology and oncology have led to the rapid growth of biologic therapeutics. Their success has resulted in significant changes to virtually every step in the drug discovery and development process. Biologics are produced by living organisms, and screening libraries are generated by immunization or phage display. Lead optimization utilizes sophisticated protein engineering to improve drug-like properties and targeting specificity. The manufacturing process for biologics is complex and requires highly specialized facilities. Determination of pharmacology and safety must overcome the complications associated with species specificity. Initial clinical testing must proceed more slowly and carefully due to the limited predictive utility of preclinical data. In summary, the drug discovery and development process has been dramatically altered by biologic therapeutics and will continue to evolve with the introduction of messenger RNA-based therapeutics and the application of artificial intelligence.

Paul McGonigle

How Biologics Have Changed the Drug Discovery Landscape

生物制剂如何改变了药物发现领域

Ryanodine receptor type 2 (RyR2) is the principal intracellular calcium release channel in the cardiac sarcoplasmic reticulum (SR). Pathological RyR2 hyperactivity generates arrhythmia risk in genetic and structural heart diseases. RYR2 gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia. In structural heart diseases (i.e., heart failure), posttranslation modifications render RyR2 channels leaky, resulting in pathologic calcium release during diastole, contributing to arrhythmogenesis and contractile dysfunction. Hence, RyR2 represents a therapeutic target in arrhythmogenic heart diseases. We provide an overview of the structure and function of RyR2, and then review US Food and Drug Administration–approved and investigational RyR2 inhibitors. A therapeutic classification of RyR2 inhibitors is proposed based on their mechanism of action. Class I RyR2 inhibitors (e.g., flecainide) do not change SR calcium content and are primarily antiarrhythmic. Class II RyR2 inhibitors (e.g., dantrolene) increase SR calcium content, making them less effective as antiarrhythmics but preferable in conditions with reduced SR calcium content such as heart failure.

Tri Q. Do

Björn C. Knollmann

Inhibitors of Intracellular RyR2 Calcium Release Channels as Therapeutic Agents in Arrhythmogenic Heart Diseases

细胞内RyR2钙释放通道抑制剂作为心律失常性心脏疾病的疗法

The last two decades have witnessed substantial advances in identifying synaptic plasticity responsible for behavioral changes in animal models of substance use disorder. We have learned the most about cocaine-induced plasticity in the nucleus accumbens and its relationship to cocaine seeking, so that is the focus in this review. Synaptic plasticity pointing to potential therapeutic targets has been identified mainly using two drug self-administration models: extinction-reinstatement and abstinence models. A relationship between cocaine seeking and potentiated AMPAR transmission in nucleus accumbens is indicated by both models. In particular, an atypical subpopulation—Ca2+-permeable or CP-AMPARs—mediates cue-induced seeking that persists even after long periods of abstinence, modeling the persistent vulnerability to relapse that represents a major challenge in treating substance use disorder. We review strategies to reverse CP-AMPAR plasticity; strategies targeting other components of excitatory synapses, including dysregulated glutamate uptake and release; and behavioral interventions that can be augmented by harnessing synaptic plasticity.

Marina E. Wolf

Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics

靶向神经可塑性在物质使用障碍中的作用：对治疗的启示

Obesity is a global health concern. Progress in understanding the physiology of obesity and weight reduction has provided new drug targets. Development and testing of new antiobesity medications (AOMs) has the potential to quickly expand options for treatment. In this review, we briefly summarize the physiology of obesity and weight reduction, as well as medications currently approved for weight management. We highlight the increasing use of incretin and nutrient-stimulated hormone-based therapies. We conclude with an overview of AOMs progressing through the pipeline and discuss their implications for the rapidly evolving field of obesity management.

Ariana M. Chao

Simeon Taylor

Molly Moore

Anastassia Amaro

Thomas A. Wadden

Evolving Approaches for Pharmacological Therapy of Obesity

肥胖药物治疗的演变方法

Genetically driven clinical trial enrichment has been proposed to accelerate and reduce the cost of developing new therapeutics. Usage of this approach has not been comprehensively reviewed. We searched Ovid MEDLINE, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and WHO ICTRP for articles published between 2010 and 2023. Excluding absorption, distribution, metabolism, and elimination pharmacogenetic studies and anti-infectives, we found 95 completed, 4 terminated, and 22 ongoing prospective genetically enriched trials on 110 drugs for 48 nononcology, nonrare syndromic indications. Trial sizes ranged from 4 to 6,147 participants (median 72) and covered numerous disease areas, particularly neurology (30), metabolism (22), and psychiatry (17). Fifty-six completed studies (60%) met their primary end point. Overall, this scoping review demonstrates that genetically enriched trials are feasible and scalable across disease areas and provide critical information for further development, or attrition, of investigational drugs. Large, appropriately designed disease-, hospital-, or population-based biobanks will undoubtedly facilitate this type of precision drug development approach.

Abbreviation	Annu. Rev. Pharmacol. Toxicol.
Journal Impact	11.18
Quartiles(Global)	TOXICOLOGY(Q1)

ISSN	0362-1642, 1545-4304
h-index	224

Publication Information	Publisher: Annual Reviews Inc.，Publishing cycle: Annual，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1975，Proportion of original research papers: 0.00%，Self Citation Rate:0.00%， Gold OA Rate: 33.66%
Average review cycle	网友分享经验：约稿?周期不定
Average recruitment ratio	网友分享经验：约稿形式

Annual Review of Pharmacology and Toxicology

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