A personal view of pharmacology.

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

authors： Vermeij WP,Hoeijmakers JH,Pothof J

更新日期：2016-01-01 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

authors： White RE

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

authors： Goldman SM

更新日期：2014-01-01 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

authors： Patel HH,Murray F,Insel PA

更新日期：2008-01-01 00:00:00

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

authors： Dray A,Urban L

更新日期：1996-01-01 00:00:00

abstract：:Most facets of mammalian physiology and behavior vary according to time of day, thanks to endogenous circadian clocks. Therefore, it is not surprising that many aspects of pharmacology and toxicology also oscillate according to the same 24-h clocks. Daily oscillations in abundance of proteins necessary for either drug...

journal_title：Annual review of pharmacology and toxicology

authors： Dallmann R,Brown SA,Gachon F

更新日期：2014-01-01 00:00:00

abstract：:In this review, we discuss the potential pharmacological targeting of a set of powerful epigenetic mechanisms: DNA methylation control systems in the central nervous system (CNS). Specifically, we focus on the possible use of these targets for novel future treatments for learning and memory disorders. We first describ...

journal_title：Annual review of pharmacology and toxicology

authors： Day JJ,Kennedy AJ,Sweatt JD

更新日期：2015-01-01 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

authors： Wei LN

更新日期：2003-01-01 00:00:00

abstract：:Recent studies of membrane transporters have revealed their importance in determining the pharmacokinetics of transporter substrates. When drug-drug interactions (DDIs) or genetic polymorphisms (i.e., pharmacogenetics) affect the activities of transporters, the pharmacokinetics of transporter substrate drugs is altere...

journal_title：Annual review of pharmacology and toxicology

authors： Yoshida K,Maeda K,Sugiyama Y

更新日期：2013-01-01 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

authors： DeGorter MK,Xia CQ,Yang JJ,Kim RB

更新日期：2012-01-01 00:00:00

abstract：:Organophosphorus insecticide self-poisoning is a major global health problem, killing over 100,000 people annually. It is a complex multi-organ condition, involving the inhibition of cholinesterases, and perhaps other enzymes, and the effects of large doses of ingested solvents. Variability between organophosphorus in...

journal_title：Annual review of pharmacology and toxicology

authors： Eddleston M

更新日期：2019-01-06 00:00:00

abstract：:The beta 3 subtype of adrenaline and noradrenaline receptors has now been extensively characterized at the structural and functional levels. Ligand binding and adenylyl cyclase activation studies helped define a beta-adrenergic profile that is quite distinct from that of the beta 1- and beta 2-adrenergic receptors, bu...

journal_title：Annual review of pharmacology and toxicology

authors： Strosberg AD

更新日期：1997-01-01 00:00:00

abstract：:Recent advances in cell signaling research suggest that multiple sets of signal transducing molecules are preorganized and sequestered in distinct compartments within the cell. These compartments are assembled and maintained by specific cellular machinery. The molecular ecology within a compartment creates an environm...

journal_title：Annual review of pharmacology and toxicology

authors： White MA,Anderson RG

更新日期：2005-01-01 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

authors： Welsh DG,Tran CHT,Hald BO,Sancho M

更新日期：2018-01-06 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

authors： Finnell RH,Waes JG,Eudy JD,Rosenquist TH

更新日期：2002-01-01 00:00:00

abstract：:The renin-angiotensin-aldosterone system is one of the most important systems in cardiovascular control and in the pathogenesis of cardiovascular diseases. Therefore, it is already a very successful drug target for the therapy of these diseases. However, angiotensins are generated not only in the plasma but also local...

journal_title：Annual review of pharmacology and toxicology

authors： Bader M

更新日期：2010-01-01 00:00:00

abstract：:Either an excess or a deficiency of vitamin A and related compounds (retinoids) causes abnormal morphological development (teratogenesis). Potential retinoid sources come from dietary intake, nutritional supplements, and some therapeutic drugs. Therefore, understanding the mechanisms of retinoid teratogenesis is impor...

journal_title：Annual review of pharmacology and toxicology

authors： Collins MD,Mao GE

更新日期：1999-01-01 00:00:00

abstract：:Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published cli...

journal_title：Annual review of pharmacology and toxicology

authors： Sharma R,Bose D,Maminishkis A,Bharti K

更新日期：2020-01-06 00:00:00

abstract：:The Risk Assessment Committee of the European Chemicals Agency issued an opinion on classifying titanium dioxide (TiO2) as a suspected human carcinogen upon inhalation. Recent animal studies indicate that TiO2 may be carcinogenic through the oral route. There is considerable uncertainty on the carcinogenicity of TiO2,...

journal_title：Annual review of pharmacology and toxicology

authors： Braakhuis HM,Gosens I,Heringa MB,Oomen AG,Vandebriel RJ,Groenewold M,Cassee FR

更新日期：2021-01-06 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

authors： Li L,Tran D,Zhu H,Balimane P,Willett G,Zhao P,Gerrard SE,Vogelsong KM,Wang Y,Seo SK

更新日期：2021-01-06 00:00:00

abstract：:Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular saf...

journal_title：Annual review of pharmacology and toxicology

authors： Magdy T,Schuldt AJT,Wu JC,Bernstein D,Burridge PW

更新日期：2018-01-06 00:00:00

abstract：:The presence of druggable, topographically distinct allosteric sites on a wide range of receptor families has offered new paradigms for small molecules to modulate receptor function. Moreover, ligands that target allosteric sites offer significant advantages over the corresponding orthosteric ligands in terms of selec...

journal_title：Annual review of pharmacology and toxicology

authors： Wenthur CJ,Gentry PR,Mathews TP,Lindsley CW

更新日期：2014-01-01 00:00:00

abstract：:The promise of drug repurposing is to accelerate the translation of knowledge to treatment of human disease, bypassing common challenges associated with drug development to be more time- and cost-efficient. Repurposing has an increased chance of success due to the previous validation of drug safety and allows for the ...

journal_title：Annual review of pharmacology and toxicology

authors： Pulley JM,Rhoads JP,Jerome RN,Challa AP,Erreger KB,Joly MM,Lavieri RR,Perry KE,Zaleski NM,Shirey-Rice JK,Aronoff DM

更新日期：2020-01-06 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

authors： Rudraiah S,Zhang X,Wang L

更新日期：2016-01-01 00:00:00

abstract：:Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included...

journal_title：Annual review of pharmacology and toxicology

authors： Vane JR,Bakhle YS,Botting RM

更新日期：1998-01-01 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

authors： García-Nafría J,Tate CG

更新日期：2020-01-06 00:00:00

abstract：:The realization that there exists a multimembered family of cation channels with structural similarity to Drosophila's Trp channel emerged during the second half of the 1990s. In mammals, depending on the species, the TRP family counts 29 or 30 members which has been subdivided into 6 subfamilies on the basis of seque...

journal_title：Annual review of pharmacology and toxicology

authors： Birnbaumer L

更新日期：2009-01-01 00:00:00

abstract：:Both pharmacologic and genetic methods are now available to manipulate intracellular levels of the protein thiol metallothionein. These approaches have begun to reveal the protective roles metallothioneins (MTs) have against oxygen, nitrogen, and carbon-centered free radicals, as well as the contributory role of MT to...

journal_title：Annual review of pharmacology and toxicology

authors： Lazo JS,Pitt BR

更新日期：1995-01-01 00:00:00

abstract：:Mechanism-based PK-PD models differ from conventional PK-PD models in that they contain specific expressions to characterize, in a quantitative manner, processes on the causal path between drug administration and effect. This includes target site distribution, target binding and activation, pharmacodynamic interaction...

journal_title：Annual review of pharmacology and toxicology

authors： Danhof M,de Jongh J,De Lange EC,Della Pasqua O,Ploeger BA,Voskuyl RA

更新日期：2007-01-01 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

authors： Fernandez EJ,Lolis E

更新日期：2002-01-01 00:00:00