Abstract：
:Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors are a class of lipid-lowering medications, with a major activity on plasma cholesterol levels, now enjoying a vast popularity among physicians and patients. These drugs, affecting a very early and key step of sterol biosynthesis, differ to a large extent in their physicochemical properties, tissue distribution and side effects in animals, possibly in humans. Some of these agents (namely lovastatin and simvastatin) are strikingly lipophilic and require enzymatic conversion from the lactone to the open-ring forms, whereas pravastatin, active per se, is hydrophilic. Liver uptake of pravastatin is regulated by a carrier-mediated mechanism. Other HMG CoA reductase inhibitors have been designed, with the objective of obtaining high levels of hepato-selectivity. Evaluation of available data in terms of potential advantages in tissue, namely liver selectivity, of HMG CoA reductase inhibitors, suggests, that, indeed, altered sterol biosynthesis in a number of tissues may potentially result in the appearance of significant side effects. While there is no clear-cut relationship between tissue selectivity and lipophilicity, the presence of this latter feature seems, in general, to dictate a lesser absorption to peripheral tissues vs the liver. At present, the toxicological profile of major HMG CoA reductase inhibitors appears safe; it is, however, possible that in selected patient groups liver selectivity may offer a considerable therapeutic advantage.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Sirtori CRdoi
10.1016/0163-7258(93)90031-8subject
Has Abstractpub_date
1993-12-01 00:00:00pages
431-59issue
3eissn
0163-7258issn
1879-016Xpii
0163-7258(93)90031-8journal_volume
60pub_type
杂志文章,评审abstract：:Despite the advances in tumor identification and treatment, cancer remains the primary driver of death around the world. Also, regular treatments for the disease are incapable of targeting particular cancer types at different stages since they are not specifically focused on harmful cells since they influence both sol...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.10.010
更新日期：2018-03-01 00:00:00
abstract：:Exacerbations of asthma are the main cause of asthma morbidity. They induce acute respiratory failure, and sometimes death. Two immunological signals acting in synergy are necessary for inducing asthma exacerbations. The first, triggered by allergens and/or unknown agents leads to the chronic Th2 inflammation characte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.03.010
更新日期：2011-07-01 00:00:00
abstract：:Dipeptidyl peptidase 4 (DPP4, DPPIV, CD26, EC 3.4.14.5) was discovered more than four decades ago as a serine protease that cleaves off N-terminal dipeptides from peptide substrates. The development of potent DPP4 inhibitors during the past two decades has led to the identification of DPP4 as a target in the treatment...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.07.012
更新日期：2012-12-01 00:00:00
abstract：:The integration of retroviral DNA appears to be obligatory for the efficient replication of retroviruses in their respective host cells. During a natural infection, integration takes place in a process that includes biochemically and temporally discrete steps. These are: (1) the removal of two nucleotides from the 3' ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90062-0
更新日期：1994-01-01 00:00:00
abstract：:Flavonoids are natural polyphenolic compounds which are included in a panoply of drugs and used to treat and/or manage human ailments such as metabolic, cardiovascular, neurological disorders and cancer. Thus, the purpose of this review is to emphasize the importance of flavonoids for the treatment of autoimmune disea...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.09.009
更新日期：2019-02-01 00:00:00
abstract：:Increasing epidemiological and experimental evidence implicates gestational infections as one important factor involved in the pathogenesis of several neuropsychiatric disorders. Corresponding preclinical model systems based upon maternal immune activation (MIA) by treatment of the pregnant female have been developed....
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.01.001
更新日期：2015-05-01 00:00:00
abstract：:In addition to their prominent roles in the control of reproduction, estrogens are important modulators of energy balance, as evident in conditions of deficiency of estrogens, which are characterized by increased feeding and decreased energy expenditure, leading to obesity. AMP-activated protein kinase (AMPK) is a ubi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.03.014
更新日期：2017-10-01 00:00:00
abstract：:Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs duri...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.09.007
更新日期：2011-02-01 00:00:00
abstract：:It is now generally accepted that protein phosphorylation-dephosphorylation has a role in the regulation of essentially all cellular functions. Thus, it is of interest that this process is involved in signal transduction. Nonetheless, the extent to which protein phosphorylation participates in signaling is truly remar...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00056-4
更新日期：1999-05-01 00:00:00
abstract：:RANKL is a key molecule that bridges the bone and immune systems. RANKL stimulation activates a signaling pathway downstream of RANK, thereby determining the extent of bone resorption by inducing osteoclast maturation. The signaling pathway also regulates the development of different lymphoid organs, including the thy...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107682
更新日期：2021-02-01 00:00:00
abstract：:This review provides biochemical, analytical, and biological background information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as an emerging target for the design of low-molecular-weight antifungals. The article includes the following: (1) a biochemical description of HexNAc'ase (reaction catal...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00110-1
更新日期：1997-10-01 00:00:00
abstract：:In the 1980s, Bowery and colleagues discovered the presence of a novel, bicuculline-resistant and baclofen-sensitive type of GABA receptor on peripheral nerve terminals, the GABA(B) receptor. Since this pioneering work, GABA(B) receptors have been identified in the Central Nervous System (CNS), where they provide an i...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.06.004
更新日期：2011-11-01 00:00:00
abstract：:P2Y12 receptor inhibition in addition to aspirin is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI). Despite advances in contemporary antithrombotic therapy, periprocedural thrombotic complications such as myocardial infarction ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.01.004
更新日期：2016-03-01 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：:Nucleoside monophosphate kinases catalyze the reversible phosphotransferase reaction between nucleoside triphosphates and monophosphates, i.e., monophosphates are converted to their corresponding diphosphate form. These enzymes play an important role in the synthesis of nucleotides that are required for a variety of c...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00048-6
更新日期：2000-08-01 00:00:00
abstract：:Necrosis of skeletal muscle is produced by two types of snake venom components: single chain peptides consisting of 42-44 amino acid residues and phospholipases A2 representing either single chain proteins or existing as complexes of several enzyme subunits or combined with other nonenzymatic proteins. Vacuolation, ly...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90081-c
更新日期：1990-01-01 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：:New techniques for the analysis of proteins with specific binding for natural retinoids in human plasma and skin extracts have been developed. Polyacrylamide gel electrophoresis (PAGE), followed by protein blotting with an antiserum specific to retinol-binding protein (RBP), the plasma carrier of retinol, showed that:...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(89)90073-9
更新日期：1989-01-01 00:00:00
abstract：:There is substantial molecular evidence for the involvement of beta1 integrin in tissue organisation and remodelling, which confers a key role in cell growth, differentiation, migration, and survival. This role has been, in part, highlighted using the transgenic approach which does little to define the more subtle fun...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.07.002
更新日期：2008-11-01 00:00:00
abstract：:Dopamine D2 autoreceptors (D2ARs), located in somatodendritic and axon terminal compartments of dopamine (DA) neurons, function to provide a negative feedback regulatory control on DA neuron firing, DA synthesis, reuptake and release. Dysregulation of D2AR-mediated DA signaling is implicated in vulnerability to substa...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107583
更新日期：2020-09-01 00:00:00
abstract：:Targeted therapies have changed the landscape of treatments for non-small cell lung cancer (NSCLC). Specific targeted therapies have been approved for NSCLC patients harboring genetic alterations in four oncogenes, and agents targeting additional oncogenic drivers are under investigation. Standard first-line chemother...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.08.007
更新日期：2019-01-01 00:00:00
abstract：:Neurosteroids are neuroactive brain-born steroids. They can act through non-genomic and/or through genomic pathways. Genomic pathways are largely described for steroid hormones: the binding to nuclear receptors leads to transcription regulation. Pregnenolone, Dehydroepiandrosterone, their respective sulfate esters and...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.06.011
更新日期：2018-11-01 00:00:00
abstract：:The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90-kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00013-8
更新日期：1998-08-01 00:00:00
abstract：:Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.06.009
更新日期：2015-10-01 00:00:00
abstract：:This review takes a translational neuroscience perspective on the role of glutamate systems in human ethanol abuse and dependence. Ethanol is a simple molecule with profound effects on many chemical systems in the brain. Glutamate is the primary excitatory neurotransmitter in the brain. Glutamatergic systems are targe...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(03)00054-8
更新日期：2003-07-01 00:00:00
abstract：:Activated platelets contribute to plaque formation within blood vessels in the early and late stages of atherogenesis, and therefore they have been proposed as risk factor for cardiovascular disease. Anti-platelet drugs, such as aspirin, are now the most prescribed pharmacological treatment in Europe. Certain dietary ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.05.008
更新日期：2014-11-01 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：:In the past 4 years, RNA interference (RNAi) has become widely used as an experimental tool to analyse the function of mammalian genes, both in vitro and in vivo. By harnessing an evolutionary conserved endogenous biological pathway, first identified in plants and lower organisms, double-stranded RNA (dsRNA) reagents ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.004
更新日期：2005-08-01 00:00:00
abstract：:Aquaporin (AQP) water and solute channels have basic physiological functions throughout the human body. AQP-facilitated water permeability across cell membranes is required for rapid reabsorption of water from pre-urine in the kidneys and for sustained near isosmolar water fluxes e.g. in the brain, eyes, inner ear, an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.08.002
更新日期：2015-11-01 00:00:00
abstract：:Enzymes of the UDP-glucuronosyltransferase (UGT) superfamily contribute to the elimination of drugs from almost all therapeutic classes. Awareness of the importance of glucuronidation as a drug clearance mechanism along with increased knowledge of the enzymology of drug and chemical metabolism has stimulated interest ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107689
更新日期：2021-02-01 00:00:00
