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 over fifty years has covered the breadth of neurotransmitters and related substances, focusing on the discovery and characterization of novel messenger molecules. I can't conceptualize a more rewarding professional life.
journal_name
Annu Rev Pharmacol Toxicoljournal_title
Annual review of pharmacology and toxicologyauthors
Snyder SHdoi
10.1146/annurev-pharmtox-010716-104511subject
Has Abstractpub_date
2017-01-06 00:00:00pages
1-11eissn
0362-1642issn
1545-4304journal_volume
57pub_type
历史文章,杂志文章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
pub_type: 杂志文章
doi:10.1146/annurev-pharmtox-031120-015212
更新日期:2021-01-06 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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.010909.105844
更新日期:2010-01-01 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::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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.47.120505.105154
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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.30.040190.001011
更新日期:1990-01-01 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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.40.1.335
更新日期:2000-01-01 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::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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.36.040196.002455
更新日期:1996-01-01 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
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::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::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
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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.40.1.649
更新日期:2000-01-01 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::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
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010814-124316
更新日期:2016-01-01 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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.35.040195.003223
更新日期:1995-01-01 00:00:00
abstract::The theme "New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development" links 13 articles in this volume of the Annual Review of Pharmacology and Toxicology (ARPT). The engaging prefatory articles by Arthur Cho and Robert Lefkowitz set the stage for this theme and for the revie...
journal_title:Annual review of pharmacology and toxicology
pub_type:
doi:10.1146/annurev-pharmtox-092617-121952
更新日期:2018-01-06 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
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-011112-140309
更新日期:2013-01-01 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
pub_type: 杂志文章
doi:10.1146/annurev-pharmtox-010919-023645
更新日期:2021-01-06 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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.46.120604.141238
更新日期:2006-01-01 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
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010814-124649
更新日期:2015-01-01 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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.41.1.593
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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.39.1.399
更新日期:1999-01-01 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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.48.113006.094646
更新日期:2008-01-01 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
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010818-021050
更新日期:2019-01-06 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
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010716-104846
更新日期:2017-01-06 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
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010617-053110
更新日期:2018-01-06 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::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
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.45.120403.095807
更新日期:2005-01-01 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
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010919-023537
更新日期:2020-01-06 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
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010611-134525
更新日期:2014-01-01 00:00:00