Mechanisms of action of bisphosphonates.

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：: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：: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：: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

authors： Coffey JW,Gaiha GD,Traverso G

更新日期：2021-01-06 00:00:00

abstract：:Imidazoline (I) receptors constitute a family of nonadrenergic high-affinity binding sites for clonidine, idazoxan, and allied drugs. One major subclass, the I1 receptors, whose subcellular distribution and signal transduction mechanisms are uncertain, partly mediates the central hypotensive actions of clonidine-like ...

journal_title：Annual review of pharmacology and toxicology

authors： Regunathan S,Reis DJ

更新日期：1996-01-01 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：: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：: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

authors： Lee HC

更新日期：2001-01-01 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：: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：:This article provides a personal account of the discovery of the induced synthesis of drug-metabolizing enzymes and of subsequent research that led to the discovery of multiple cytochromes P450 with different catalytic activities. The manuscript also emphasizes the role of environmental factors (in addition to genetic...

journal_title：Annual review of pharmacology and toxicology

authors： Conney AH

更新日期：2003-01-01 00:00:00

abstract：:Recent discoveries of novel and potentially important biological activity have spurred interest in the chemistry and biochemistry of nitroxyl (HNO). It has become clear that, among all the nitrogen oxides, HNO is unique in its chemistry and biology. Currently, the intimate chemical details of the biological actions of...

journal_title：Annual review of pharmacology and toxicology

authors： Fukuto JM,Switzer CH,Miranda KM,Wink DA

更新日期：2005-01-01 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：: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：: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：:The cost of drugs is a major and rapidly rising component of health-care expenditures. We survey recent literature on the ethics and economics of skyrocketing pharmaceutical prices and find that advances in economic research have increased the sharpness and focus of the ethically based calls to increase access by modi...

journal_title：Annual review of pharmacology and toxicology

authors： Parker-Lue S,Santoro M,Koski G

更新日期：2015-01-01 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：: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：: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：: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：: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：: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：: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

authors： Kim D,Guengerich FP

更新日期：2005-01-01 00:00:00

abstract：:γ-Secretases are a group of widely expressed, intramembrane-cleaving proteases involved in many physiological processes. Their clinical relevance comes from their involvement in Alzheimer's disease, cancer, and other disorders. A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, de...

journal_title：Annual review of pharmacology and toxicology

authors： De Strooper B,Chávez Gutiérrez L

更新日期：2015-01-01 00:00:00

abstract：:DNA topoisomerases are double-edged swords. They are essential for many vital functions of DNA during normal cell growth. However, they are also highly vulnerable under various physiological and nonphysiological stresses because of their delicate act on breaking and rejoining DNA. These stresses (e.g. exposure to topo...

journal_title：Annual review of pharmacology and toxicology

authors： Li TK,Liu LF

更新日期：2001-01-01 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

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：: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：: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

authors： Hendrix CW,Cao YJ,Fuchs EJ

更新日期：2009-01-01 00:00:00

abstract：:Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and hav...

journal_title：Annual review of pharmacology and toxicology

authors： Bennett CF,Baker BF,Pham N,Swayze E,Geary RS

更新日期：2017-01-06 00:00:00