Abstract:
:Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.
journal_name
Annu Rev Pharmacol Toxicoljournal_title
Annual review of pharmacology and toxicologyauthors
Insel PA,Amara SG,Blaschke TF,Meyer UAdoi
10.1146/annurev-pharmtox-091616-023708subject
Has Abstractpub_date
2017-01-06 00:00:00pages
13-17eissn
0362-1642issn
1545-4304journal_volume
57pub_type
abstract::The recent advances made in elucidating the processes of nociception have altered the way that chronic pain therapy and analgesic drug development are approached. Recent studies have highlighted new targets for drug discovery, including inhibition of inflammatory mediators (kinins, growth factors), newly expressed pro...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.36.040196.001345
更新日期:1996-01-01 00:00:00
abstract::Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca(2+) messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The c...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.41.1.317
更新日期:2001-01-01 00:00:00
abstract::Electron cryo-microscopy (cryo-EM) has revolutionized structure determination of membrane proteins and holds great potential for structure-based drug discovery. Here we discuss the potential of cryo-EM in the rational design of therapeutics for membrane proteins compared to X-ray crystallography. We also detail recent...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010919-023545
更新日期:2020-01-06 00:00:00
abstract::Arterial tone is coordinated among vessel segments to optimize nutrient transport and organ function. Coordinated vasomotor activity is remarkable to observe and depends on stimuli, sparsely generated in tissue, eliciting electrical responses that conduct lengthwise among electrically coupled vascular cells. The condu...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010617-052623
更新日期:2018-01-06 00:00:00
abstract::Microbicides, substances applied topically to prevent sexual HIV infection, are needed to empower receptive sexual partners with effective prevention methods. Several large microbicide trials, however, failed to demonstrate efficacy, thus motivating a reevaluation of the current microbicide development paradigm, which...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.48.113006.094906
更新日期:2009-01-01 00:00:00
abstract::Nuclear receptors (NR) are ligand-modulated transcription factors that play diverse roles in cell differentiation, development, proliferation, and metabolism and are associated with numerous liver pathologies such as cancer, steatosis, inflammation, fibrosis, cholestasis, and xenobiotic/drug-induced liver injury. The ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010715-103209
更新日期:2016-01-01 00:00:00
abstract::Long-acting contraceptives are the most effective reversible contraceptive methods. Increasing patients' access to these contraceptives may translate into fewer unintended pregnancies and lead to substantial individual and public health benefits. However, development of long-acting products can be complex and challeng...
journal_title:Annual review of pharmacology and toxicology
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doi:10.1146/annurev-pharmtox-031120-015212
更新日期:2021-01-06 00:00:00
abstract::The application of rapid methods currently used for screening discovery drug candidates for metabolism and pharmacokinetic characteristics is discussed. General considerations are given for screening in this context, including the criteria for good screens, the use of counterscreens, the proper sequencing of screens, ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.40.1.133
更新日期:2000-01-01 00:00:00
abstract::Drug transporters are now widely acknowledged as important determinants governing drug absorption, excretion, and, in many cases, extent of drug entry into target organs. There is also a greater appreciation that altered drug transporter function, whether due to genetic polymorphisms, drug-drug interactions, or enviro...
journal_title:Annual review of pharmacology and toxicology
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doi:10.1146/annurev-pharmtox-010611-134529
更新日期:2012-01-01 00:00:00
abstract::Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a cova...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.30.040190.001011
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abstract::The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to cha...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.34.040194.001133
更新日期:1994-01-01 00:00:00
abstract::Arylamines and heterocyclic arylamines (HAAs) are of particular interest because of demonstrated carcinogenicity in animals and humans and the broad exposure to many of these compounds. The activation of these, and also some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 (P450). P450 1A2 plays a...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.45.120403.100010
更新日期:2005-01-01 00:00:00
abstract::Conflicting views abound on the peripheral neurotransmitter and neuromodulator roles of purine compounds. Substantial organ- and species-related variations have become apparent. There is, however, a body of compelling evidence for such roles, if not so broad and ubiquitous as those envisioned (7) for the central nervo...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.23.040183.002145
更新日期:1983-01-01 00:00:00
abstract::Chemokines are the largest family of cytokines in human immunophysiology. These proteins are defined by four invariant cysteines and are categorized based on the sequence around the first two cysteines, which leads to two major and two minor subfamilies. Chemokines function by activating specific G protein-coupled rec...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.42.091901.115838
更新日期:2002-01-01 00:00:00
abstract::Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010715-103801
更新日期:2016-01-01 00:00:00
abstract::CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids). These G protein-coupled receptors play an important role in many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged directly by...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.46.120604.141254
更新日期:2006-01-01 00:00:00
abstract::The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that ina...
journal_title:Annual review of pharmacology and toxicology
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doi:10.1146/annurev.pharmtox.010909.105844
更新日期:2010-01-01 00:00:00
abstract::Exposure of the developing conceptus to selected environmental agents can lead to deleterious and often times lethal birth defects. These malformations result in serious emotional and financial consequences to families and societies worldwide. As we continue to progress technologically, we face challenges from the int...
journal_title:Annual review of pharmacology and toxicology
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doi:10.1146/annurev.pharmtox.42.083001.110955
更新日期:2002-01-01 00:00:00
abstract::Systems approaches have long been used in pharmacology to understand drug action at the organ and organismal levels. The application of computational and experimental systems biology approaches to pharmacology allows us to expand the definition of systems pharmacology to include network analyses at multiple scales of ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010611-134520
更新日期:2012-01-01 00:00:00
abstract::Oral vaccination enables pain-free and self-administrable vaccine delivery for rapid mass vaccination during pandemic outbreaks. Furthermore, it elicits systemic and mucosal immune responses. This protects against infection at mucosal surfaces, which may further enhance protection and minimize the spread of disease. T...
journal_title:Annual review of pharmacology and toxicology
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更新日期:2021-01-06 00:00:00
abstract::Histone acetylation is a prominent epigenetic modification of the central nervous system that is unequivocally associated with an increase in the rate of gene transcription. Because gene transcription, in turn, plays an important role in long-lasting forms of memory, histone acetylation generally favors long-term memo...
journal_title:Annual review of pharmacology and toxicology
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doi:10.1146/annurev-pharmtox-011112-140216
更新日期:2013-01-01 00:00:00
abstract::Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations of the plasma membrane that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N and C termini, palmitolylation sites, and a scaffolding domain that facilit...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.48.121506.124841
更新日期:2008-01-01 00:00:00
abstract::Behavioral consequences of low-level lead (Pb) exposure include impairments in learning processes and in Fixed-Interval schedule-controlled operant behavior. Although the neurobiological bases of these effects remain undetermined, current evidence suggests that inhibitory effects of Pb on the NMDA receptor complex may...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.35.040195.002135
更新日期:1995-01-01 00:00:00
abstract::Retinoids regulate gene transcription by binding to the nuclear receptors, the retinoic acid (RA) receptors (RARs), and the retinoid X receptors (RXRs). RARs and RXRs are ligand-activated transcription factors for the regulation of RA-responsive genes. The actions of RARs and RXRs on gene transcription require a highl...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.43.100901.140301
更新日期:2003-01-01 00:00:00
abstract::Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered inter...
journal_title:Annual review of pharmacology and toxicology
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doi:10.1146/annurev-pharmtox-010814-124316
更新日期:2016-01-01 00:00:00
abstract::Arsenic is a naturally occurring metalloid and one of the few metals that can be metabolized inside the human body. The pervasive presence of arsenic in nature and anthropogenic sources from agricultural and medical use have perpetuated human exposure to this toxic and carcinogenic element. Highly exposed individuals ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章
doi:10.1146/annurev-pharmtox-030220-013418
更新日期:2021-01-06 00:00:00
abstract::HIV protease inhibitors, as components of combination antiretroviral drug regimens, have substantially reduced the morbidity and mortality associated with HIV infection. They selectively block the action of the virus-encoded protease and stop the virus from replicating. In general, these drugs have poor systemic bioav...
journal_title:Annual review of pharmacology and toxicology
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doi:10.1146/annurev.pharmtox.40.1.649
更新日期:2000-01-01 00:00:00
abstract::Parkinson's disease (PD) is a chronic, progressive, disabling neurodegenerative disorder that begins in mid to late life and is characterized by motor impairment, autonomic dysfunction, and, in many, psychological and cognitive changes. Recent advances have helped delineate pathogenetic mechanisms, yet the cause of PD...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-011613-135937
更新日期:2014-01-01 00:00:00
abstract::Numerous lines of evidence demonstrate that calpains, a family of 14 Ca(2+)-activated neutral cysteine proteases, are involved in oncotic cell death in a variety of models. At this time, the biochemistry of most calpains and the specific roles of different calpains in physiology and pathology remain to be determined. ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.44.101802.121804
更新日期:2004-01-01 00:00:00
abstract::Neuroglial cells of the central nervous system include the astrocytes, oligodendrocytes, and microglia. Their counterparts in the peripheral nervous system are the Schwann cells. The term neuroglia comes from an erroneous concept originally coined by Virchow (1850), in which he envisioned the neurons to be embedded in...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.39.1.151
更新日期:1999-01-01 00:00:00