Therapeutic Oligonucleotides: State of the Art.

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：: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：: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 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

authors： Drygin D,Rice WG,Grummt I

更新日期：2010-01-01 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

authors： Flexner C

更新日期：2000-01-01 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：:The heptahelical G protein-coupled receptors (GPCRs) belong to the largest family of cell surface signaling receptors encoded in the human genome. GPCRs signal to diverse extracellular stimuli and control a vast number of physiological responses, making this receptor class the target of nearly half the drugs currently...

journal_title：Annual review of pharmacology and toxicology

authors： Marchese A,Paing MM,Temple BR,Trejo J

更新日期：2008-01-01 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：:Research on autophagy and its effects on cell metabolism and physiology has increased dramatically during recent years. Multiple forms of autophagy have been characterized, and many of the genes involved in the regulation of this process have been identified. The importance of autophagy for embryonic development and m...

journal_title：Annual review of pharmacology and toxicology

authors： Orrenius S,Kaminskyy VO,Zhivotovsky B

更新日期：2013-01-01 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：: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

authors： Chen QY,Costa M

更新日期：2021-01-06 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：: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：:The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must...

journal_title：Annual review of pharmacology and toxicology

authors： Krishnamurthy P,Schuetz JD

更新日期：2006-01-01 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：: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 ...

journal_title：Annual review of pharmacology and toxicology

authors： Insel PA,Amara SG,Blaschke TF,Meyer UA

更新日期：2017-01-06 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：: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：:Mutant ras oncogenes and alterations in the mitogenic signaling pathways that they regulate are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. Of the possible approaches to inhibit Ras function, much attention has focused on a posttranslational m...

journal_title：Annual review of pharmacology and toxicology

authors： Gibbs JB,Oliff A

更新日期：1997-01-01 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：: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

authors： Aschner M,Allen JW,Kimelberg HK,LoPachin RM,Streit WJ

更新日期：1999-01-01 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：:This essay is an account of the author's experience in trying to interpret the action of drugs as seen in in vitro bioassays. The central theme is how the development of simple mathematical models has assisted in the interpretation of drug actions. Starting from encounters with partial agonists, the essay describes th...

journal_title：Annual review of pharmacology and toxicology

authors： Black J

更新日期：1996-01-01 00:00:00

abstract：:The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cue...

journal_title：Annual review of pharmacology and toxicology

authors： Levi F,Schibler U

更新日期：2007-01-01 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：: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：:The major concepts presented in this review can be summarized as follows: 1. There is a multidirectional continuum of anesthetic states--some represented by CNS excitation and others by depression. 2. The reticular activating system is influenced by all anesthetics; some inhibit its action (stage III) and some hyperex...

journal_title：Annual review of pharmacology and toxicology

authors： Winters WD

更新日期：1976-01-01 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：: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 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