Induction of drug-metabolizing enzymes: a path to the discovery of multiple cytochromes P450.

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：: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：: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

authors： Holst SC,Valomon A,Landolt HP

更新日期：2016-01-01 00:00:00

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

authors： Bevan JA,Henrion D

更新日期：1994-01-01 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

authors： Cory-Slechta DA

更新日期：1995-01-01 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：: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：: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

authors： Loh HH,Smith AP

更新日期：1990-01-01 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：: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：:Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, splice-switching ONs, and short interfering RNA drugs have been successfully developed. Moreover, antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNA decoys, DNAzymes, synthetic...

journal_title：Annual review of pharmacology and toxicology

authors： Smith CIE,Zain R

更新日期：2019-01-06 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：:The developing central nervous system (CNS) is more vulnerable to injury than the adult one. Although a great deal of research has been devoted to subtle effects of developmental exposure, such as neurobehavioral changes, this review instead focuses on a number of chemicals that have been shown, in several experimenta...

journal_title：Annual review of pharmacology and toxicology

authors： Costa LG,Aschner M,Vitalone A,Syversen T,Soldin OP

更新日期：2004-01-01 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：: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

authors： Mackie K

更新日期：2006-01-01 00:00:00

abstract：:Kv7 channels (Kv7.1-7.5) are voltage-gated K+ channels that can be modulated by five β-subunits (KCNE1-5). Kv7.1-KCNE1 channels produce the slow-delayed rectifying K+ current, IKs, which is important during the repolarization phase of the cardiac action potential. Kv7.2-7.5 are predominantly neuronally expressed and c...

journal_title：Annual review of pharmacology and toxicology

authors： Thompson E,Eldstrom J,Fedida D

更新日期：2021-01-06 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：: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：: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：:Development of scientific creativity is often tied closely to mentorship. In my case, two years with Julius Axelrod, the sum total of my research training, was transformative. My mentoring generations of graduate students and postdoctoral fellows has been as nurturing for me as it has been for them. Work in our lab ov...

journal_title：Annual review of pharmacology and toxicology

authors： Snyder SH

更新日期：2017-01-06 00:00:00

abstract：:Ion channels and G protein-coupled receptors (GPCRs) are regulated by lipids in their membrane environment. Structural studies combined with biophysical and molecular simulation investigations reveal interaction sites for specific lipids on membrane protein structures. For K channels, PIP2 plays a key role in regulati...

journal_title：Annual review of pharmacology and toxicology

authors： Duncan AL,Song W,Sansom MSP

更新日期：2020-01-06 00:00:00

abstract：:Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase of the c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. ASK1 is preferentially activated by various cytotoxic stressors and plays pivotal roles in a wide variety of cellular response to them. Recent analyses of A...

journal_title：Annual review of pharmacology and toxicology

authors： Takeda K,Noguchi T,Naguro I,Ichijo H

更新日期：2008-01-01 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：: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

authors： Gräff J,Tsai LH

更新日期：2013-01-01 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：:Determining the potential toxicity of compounds early in the drug discovery process can be extremely beneficial in terms of both time and money conservation. Because of the speed of modern chemical synthesis and screening, to accurately evaluate the large number of compounds being produced, toxicology assays must have...

journal_title：Annual review of pharmacology and toxicology

authors： Waring JF,Ulrich RG

更新日期：2000-01-01 00:00:00

abstract：:Selective, nonpeptide antagonists for tachykinin receptors first became available ten years ago. Of the three known tachykinin receptors, drug development has focused most intensively on the substance P-preferring receptor, neurokinin(1) (NK(1)). Although originally studied as potential analgesic compounds, recent evi...

journal_title：Annual review of pharmacology and toxicology

authors： Stout SC,Owens MJ,Nemeroff CB

更新日期：2001-01-01 00:00:00

abstract：:G protein-coupled receptors (GPCRs) represent a major class of proteins in the genome of many species, including humans. In addition to the mapping of a number of human disorders to regions of the genome containing GPCRs, a growing body of literature has documented frequently occurring variations (i.e. polymorphisms) ...

journal_title：Annual review of pharmacology and toxicology

authors： Rana BK,Shiina T,Insel PA

更新日期：2001-01-01 00:00:00