Abstract：
:The physiological role of K+ channel opening by endogenous substances (e.g., neurotransmitters and hormones) is a recognised inhibitory mechanism. Thus, the identification of novel synthetic molecules that 'directly' open K+ channels has led to a new direction in the pharmacology of ion channels. The existence of many different subtypes of K+ channels has been an impetus in the search for new molecules demonstrating channel and, thus, tissue selectivity. This review focuses on the different classes of openers of K+ channels, the intracellular mechanisms involved in the execution of their effects, and potential therapeutic targets.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Lawson Kdoi
10.1016/0163-7258(96)00003-4subject
Has Abstractpub_date
1996-01-01 00:00:00pages
39-63issue
1eissn
0163-7258issn
1879-016Xpii
0163725896000034journal_volume
70pub_type
杂志文章,评审abstract：:Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the therapeutic management of solid tumors, particularly ovarian cancer. Initially studied in BRCA deficient tumors, the Food and Drug Administration (FDA) indications have expanded to include other homologous recombination deficient tumors as well as bio...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107588
更新日期：2020-09-01 00:00:00
abstract：:Adenosine produces a wide variety of physiological effects through the activation of cell surface adenosine receptors (ARs). ARs are members of the G-protein-coupled receptor family, and currently, four subtypes, the A1AR, A2AAR, A2BAR, and A3AR, are recognized. This review focuses on the role of receptor structure in...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00051-0
更新日期：2000-02-01 00:00:00
abstract：:Since the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways of the brain. Dynorphins are members of the opioid peptide family and preferentially bind to kappa opioid receptors. In line with their localizat...
journal_title：Pharmacology & therapeutics
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.pharmthera.2009.05.006
更新日期：2009-09-01 00:00:00
abstract：:Destruction of the established tumour vasculature by a class of compound termed Vascular Disrupting Agents (VDAs) is showing considerable promise as a viable approach for the management of solid tumours. VDAs induce a rapid shutdown and collapse of tumour blood vessels, leading to ischaemia and consequent necrosis of ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2019.06.001
更新日期：2019-10-01 00:00:00
abstract：:Severe and prolonged impairment of mitochondrial beta-oxidation leads to microvesicular steatosis, and, in severe forms, to liver failure, coma and death. Impairment of mitochondrial beta-oxidation may be either genetic or acquired, and different causes may add their effects to inhibit beta-oxidation severely and trig...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00012-6
更新日期：1995-01-01 00:00:00
abstract：:Drug therapy directed toward the fetus would be intended for either treating a fetal disorder or improving the capacity for later intrauterine or postnatal adaptation. Most reported trials involve single cases or small numbers of fetuses receiving the drug transplacentally after the first trimester, but before attaini...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(93)90051-e
更新日期：1993-01-01 00:00:00
abstract：:The PI3K/Akt/mTOR pathway is the most frequently known activated aberrant pathway in human cancers. Pathologic activation can occur at multiple levels along the signaling pathway by a variety of mechanisms, including point mutations, amplifications, and inactivation of tumor suppressor genes. This pathway is also a kn...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.09.006
更新日期：2015-02-01 00:00:00
abstract：:Three major types of opioid receptors, designated mu, delta, and kappa, are widely expressed in the CNS. Development of selective receptor ligands and recent cloning of each receptor have contributed greatly to our increasing knowledge of the neuropharmacological profile of each opioid receptor type. It is of interest...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00099-1
更新日期：2001-01-01 00:00:00
abstract：:We have concentrated on how SCE is measured, how it correlates with other measures of cellular damage, and how SCE can be used as a tool to study cell cycle kinetics. We have not discussed the biological significance of SCEs, i.e. why they occur spontaneously, and what role, if any, in cellular preservation they play....
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(89)90030-2
更新日期：1989-01-01 00:00:00
abstract：:As the first-line antimalarial drugs, artemisinins gained wide acceptance after the emergence of resistance to chloroquine in the 1950s. Artemisinin-based drugs have saved lives, especially in developing countries. The discovery of artemisinin was unique, timely, and fascinating, and the benefits of artemisinin were w...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107658
更新日期：2020-12-01 00:00:00
abstract：:Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.08.002
更新日期：2018-02-01 00:00:00
abstract：:Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activati...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90015-r
更新日期：1992-01-01 00:00:00
abstract：:The pharmaceutical industry offers the world's population alleviation and cure from a variety of medical conditions, while also contributing to the economic performance of many countries. The potential importance of these characteristics have made the industry an area of intense debate, criticism and praise. This revi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00002-x
更新日期：1995-05-01 00:00:00
abstract：:Nerve growth factor (NGF) and other members of the neurotrophin family are critical for the survival and differentiation of neurons and have been implicated in the pathophysiology of numerous disease states. Although the therapeutic potential of neurotrophins has generated much excitement over the past decade, inconve...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.03.005
更新日期：2007-08-01 00:00:00
abstract：:Functional polymorphisms that alter gene expression and mRNA processing appear to play a critical role in shaping human phenotypic variability. Intensive studies on polymorphisms affecting drug response have revealed multiple modes of altered gene function, frequently involving cis-acting regulatory sequence variants....
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.11.001
更新日期：2005-04-01 00:00:00
abstract：:Angiotensin II (Ang II) is the main effector hormone of the renin-angiotensin system (RAS). The pathogenesis of many cardiovascular diseases, including heart failure and hypertension, appear to be related to Ang II production. The generation of Ang II involves angiotensin-converting enzyme (ACE) in circulating and tis...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00021-1
更新日期：1997-01-01 00:00:00
abstract：:Multiple sclerosis (MS) is the commonest cause of progressive neurological disability amongst young, Caucasian adults. MS is considered to be an auto-immune disease that results from an attack against myelin, the layer which surrounds axons. The pathophysiology of MS is complex, with both demyelination and axonal dege...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.01.006
更新日期：2010-04-01 00:00:00
abstract：:While antibiotics revolutionized the treatment of infectious disease in the 20th century, bacterial resistance now threatens to render many of them ineffective. Aminoglycosides are a class of clinically important antibiotics used in the treatment of infections caused by Gram-positive and -negative organisms. They are ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00197-3
更新日期：2002-02-01 00:00:00
abstract：:Forward Pharmacology seeks to identify small or large molecules that modulate a normal or abnormal biological process in living cells or whole organisms and historically has been responsible for the discovery of many clinically used drugs. Forward Pharmacology approaches have become particularly attractive because adv...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.002
更新日期：2005-08-01 00:00:00
abstract：:The chewing of the stimulant leaf khat is a habit that is widespread in certain countries of East Africa and the Arabian peninsula. During the last decade, important progress has been made in understanding the pharmacological basis for the effects of khat. It is now known that the CNS action of this drug is due to the...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90057-9
更新日期：1990-01-01 00:00:00
abstract：:Adipocyte hyperplasia occurs by the proliferation and differentiation of adipocyte precursor cells or preadipocytes. Although the process of commitment to the adipocyte lineage is poorly understood, a great deal of information has accumulated about the processes and regulatory mechanisms involved in preadipocyte diffe...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90018-3
更新日期：1994-01-01 00:00:00
abstract：:The RNA-dependent P1/eIF-2 alpha protein kinase is a highly specific protein-serine/threonine kinase that catalyzes the phosphorylation of the alpha subunit of protein synthesis initiation factor eIF-2. The kinase plays a central role in translational control. The activity of the kinase is regulated by a variety of na...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90005-k
更新日期：1992-01-01 00:00:00
abstract：:Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by pathophysiological factors including airflow limitation, hyperinflation and reduced gas exchange. Treatment consists of lifestyle changes, lung rehabilitation and pharmacological therapies such as long acting beta-2-agonists (L...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.05.007
更新日期：2017-11-01 00:00:00
abstract：:Metabolic diseases have a tremendous impact on human morbidity and mortality. Numerous targets regulating adenosine monophosphate kinase (AMPK) have been identified for treating the metabolic syndrome (MetS), and many compounds are being used or developed to increase AMPK activity. In parallel, the cyclic nucleotide p...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107475
更新日期：2020-04-01 00:00:00
abstract：:Numerous pro-inflammatory cytokines have been implicated in the pathogenesis of several cardiovascular diseases. Interleukin (IL)-33 is a new member of the IL-1 family of cytokines that promotes Th2 type immune responses by signaling through the ST2L and IL-1RAcP dimeric receptor complex. Furthermore, the biological e...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.02.005
更新日期：2011-08-01 00:00:00
abstract：:Unless it is carefully controlled, bias often distorts the results of clinical trials, usually exaggerating the magnitude of true efficacy. For that reason, procedures to limit bias have been mandated by the FDA when assessing efficacy in clinical trials. The present review shows that the effects of bias in preclinica...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.05.002
更新日期：2007-07-01 00:00:00
abstract：:For many years, acid-suppressive therapy has been at the forefront of treating gastroesophageal reflux disease (GERD), yet despite the advent of the proton pump inhibitors (PPIs) some patients continue to experience persistent GERD symptoms. Therapeutic (non-surgical) options for such patients are currently limited. T...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.02.008
更新日期：2009-06-01 00:00:00
abstract：:Metabolic syndrome has been described as the association of insulin resistance, hypertension, hyperlipidemia and obesity. Its prevalence increased dramatically, mainly in developed countries. Animal models are essential to understand the pathophysiology of this syndrome. This review presents the murine models of metab...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.11.004
更新日期：2013-03-01 00:00:00
abstract：:The vascular system develops during embryonic development by at least two distinct processes; vasculogenesis is the development of blood vessels from in situ differentiating angioblasts and angiogenesis is the sprouting of capillaries from pre-existing vessels. The molecular mechanisms involved in the regulation of th...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(91)90066-u
更新日期：1991-01-01 00:00:00
abstract：:There are various receptor tyrosine kinase (TK)-targeted drugs that are currently used in the treatment of patients with non-small cell lung cancer (NSCLC). Among them, the epidermal growth factor receptor (EGFR) TK inhibitors (TKIs) are the most extensively studied. Receptor TKIs including EGFR TKIs have shown dramat...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.03.002
更新日期：2016-05-01 00:00:00
