Abstract:
:The molecular mechanisms of 3 genetic polymorphisms of drug metabolism have been studied at the level of enzyme activity, enzyme protein and RNA/DNA. As regards debrisoquine/sparteine polymorphism, cytochrome P-450IID6 was absent in livers of poor metabolizers; aberrant splicing of premRNA of P-450IID6 may be responsible for this. Moreover, 3 mutant alleles of the P-450IID6 locus on chromosome 22 associated with the poor metabolizer phenotype were identified by Southern analysis of leucocyte DNA. The presence of 2 identified mutant alleles allowed the prediction of the phenotype in approximately 25% of poor metabolizers. The additional gene-inactivating mutations which are operative in the remainder of poor metabolizers are now being studied. Regarding mephenytoin polymorphism, although the deficient reaction, S-mephenytoin 4'-hydroxylation, has been well defined in human liver microsomes, the mechanism of this polymorphism remains unclear. All antibodies prepared to date against cytochrome P-450 fractions with this activity recognize several structurally similar enzymes and several cDNAs related to these enzymes have been isolated and expressed in heterologous systems. However, which isozyme is affected by this polymorphism is not known. As regards N-acetylation polymorphism, N-acetyltransferases have been purified from human liver, specific antibodies prepared; it was observed that immunoreactive N-acetyltransferase is decreased or undetectable in liver of "slow acetylators". Two genes that encode functional N-acetyltransferase were characterized. The product of one of these genes has identical activity and characteristics as the polymorphic liver enzyme. Cloned DNA from rapid and slow acetylator individuals has been analyzed to identify the structural or regulatory defect that causes deficient N-acetyltransferase.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
Meyer UAdoi
10.1111/j.1472-8206.1990.tb00041.xsubject
Has Abstractpub_date
1990-01-01 00:00:00pages
595-615issue
6eissn
0767-3981issn
1472-8206journal_volume
4pub_type
杂志文章,评审abstract::Amitriptyline significantly inhibited alcohol, aspirin, indomethacin and cold-restraint stress-induced ulceration. Secretory studies conducted in pyloric-ligated rats revealed that the drug, at the doses employed, significantly reduced total acidity and protein content. However, significant reductions of the gastric v...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1472-8206.2002.00092.x
更新日期:2002-08-01 00:00:00
abstract::The aim of phase I studies per se is to explore the tolerance of new compounds which have demonstrated a certain level of activity in animals at sufficiently low non-toxic doses. In most cases, these studies are conducted in 2 steps in a limited number of healthy male volunteers: a single rising dose study followed by...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.1990.tb00064.x
更新日期:1990-01-01 00:00:00
abstract::Multiple standard software packages for population pharmacokinetics (PK) modeling are currently available. These programs may significantly vary in the algorithms used for modeling plasma concentrations as a function of time course. We compared the population PK parameters obtained by using two standard software packa...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2008.00641.x
更新日期:2009-02-01 00:00:00
abstract::This study evaluated the effect of lacosamide (LCM) on biochemical and mitochondrial parameters after PTZ kindling in mice. Male mice were treated on alternative days for a period of 11 days with LCM (20, 30, or 40 mg/kg), saline, or diazepam (2 mg/kg), before PTZ administration (50 mg/kg). The hippocampi were collect...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12598
更新日期:2020-08-09 00:00:00
abstract::High-dose benzodiazepine (BDZs) represents an important risk factor for dependence, particularly in a prison environment. In Lyon's prison, BDZs and/or opioid maintenance treatment are often prescribed to patients with mental disorders. The aim of this retrospective study was to assess the impact of psychiatrist and p...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2010.00902.x
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abstract::Thienopyridines have become the cornerstone of treatment for percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y12 inhibitors are more potent, more predictable, and have a faster onset of action than clopidogrel, cha...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2011.00984.x
更新日期:2012-02-01 00:00:00
abstract::The aim of this study was to investigate which principal human cytochrome P450 (CYP450) enzymes are affected by artemisinin and to what degree the artemisinin derivatives differ with respect to their respective induction and inhibition capacity. Seventy-five healthy adults were randomized to receive therapeutic oral d...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1472-8206.2007.00471.x
更新日期:2007-06-01 00:00:00
abstract::Abstract The relationship between depression and dopamine deficiency in the mesolimbic pathway has been hypothesized for many years. The experimental studies with animal models of depression and the human studies implicate the role of the dopamine system in depression. Not only do dopaminergic receptor agonists, but a...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2004.00287.x
更新日期:2004-12-01 00:00:00
abstract::Rhodamine 123 is a fluorescent cationic dye commonly used as a mitochondrial probe and known or suspected to be transported by certain drug membrane transporters. The present study was designed to characterize the putative interactions of rhodamine 123 with human organic cation transporter (OCT) 1 and OCT2. Intracellu...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2012.01071.x
更新日期:2014-02-01 00:00:00
abstract::We report 6 additional observations of a drug/hormone assay interaction between serum testosterone and phenylbutazone intake. This interaction had been described previously only once. We discuss its potential mechanisms, based upon our experimental findings, and its clinical implications. ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2007.00564.x
更新日期:2008-04-01 00:00:00
abstract::The efficacy of silymarin treatment in preventing biochemical and histological alterations in CCL4-induced liver cirrhosis in rats was studied. Four groups of rats were treated with: (1) CCL4; (2) mineral oil; (3) CCL4 + silymarin; and (4) silymarin. All animals were sacrificed 72 h after the end of treatments. The ac...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1989.tb00449.x
更新日期:1989-01-01 00:00:00
abstract::We investigated the underlying mechanisms of penehyclidine hydrochloride (PHC), a novel selective anticholinergic drug on isolated rat uterus. The method of radio-immunity assay was further employed to determine cyclic adenosine mono phosphate (cAMP) levels in isolated rat uterus for comparing with selective effect on...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2009.00712.x
更新日期:2009-08-01 00:00:00
abstract::We estimated the effect of pentoxifylline (PTX) on the respiratory burst (examined by chemiluminescence method) of unprimed and primed neutrophils with tumor necrosis factor-alpha (TNF-alpha) in patients with stable angina pectoris. Chemiluminescence of non-stimulated as well as formyl-methionyl-leucyl-phenylalanine (...
journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1472-8206.1999.tb00345.x
更新日期:1999-01-01 00:00:00
abstract::An antagonism between cholecystokinin (CCK) peptides and benzodiazepines (BZD) has been described in various paradigms. We sought to determine whether CCK and BZD are also antagonistic in their effects on brain neurotransmitter levels in the rat. No effect on the noradrenergic system was induced in any brain area by C...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1990.tb00491.x
更新日期:1990-01-01 00:00:00
abstract::The action of ouabain, a cell membrane Na+, K+-ATPase blocker, on contractions induced by manganese ions (Mn2+) in Ca2+-free, isotonic solutions with varying concentrations of K+ in the external medium were investigated in order to evaluate the underlying role of external Na+ in Mn2+-induced contractions in isolated t...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2005.00334.x
更新日期:2005-06-01 00:00:00
abstract::We studied the effects of KATP channel blockers on [3H]GABA release in the absence of glucose in rat hippocampal slices. The omission of glucose induced a marked increase in the efflux of [3H]GABA, which was antagonized by TTX (1 microM), but not by MK 801 (1 microM) or DNQX (100 microM). Glibenclamide (10-100 microM)...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1992.tb00123.x
更新日期:1992-01-01 00:00:00
abstract::This study investigated whether simvastatin has antihypertensive activity and can enhance the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Hypertension and hypercholesterolemia were induced in rats by L-NAME and cholesterol-enriched diet, respectively. In these animals...
journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/fcp.12020
更新日期:2014-06-01 00:00:00
abstract::Previous work has shown that intraperitoneal administration of riparin III (ripIII) reduces immobility time in the forced swimming test (FST), which suggests potential antidepressant activity. As the mechanism of action is not completely understood, this study is aimed at investigating the antidepressant-like action o...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2011.00968.x
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abstract::Using an isolated non-working rat heart model, this study investigated the mechanisms of pharmacological pre-conditioning (PC) induced by P2Y receptor stimulation with pyridoxal-5'-phosphate (PLP). After 6-hydroxydopamine pretreatment and a 15-min stabilization period, isolated rat hearts were perfused for 25 min then...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2009.00677.x
更新日期:2009-06-01 00:00:00
abstract::Intracerebroventricular (i.c.v.) injections of dihydropyridine derivatives calcium channel agonist (BAY K8644) and antagonist (nifedipine, nicardipine, PN 200-110) induced opposite long-lasting changes in blood pressure (BP) in pentobarbital anesthetized spontaneously hypertensive rats (SMR). I.c.v. nifedipine (NIF), ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.1989.tb00474.x
更新日期:1989-01-01 00:00:00
abstract::The effects of two single oral doses (5 mg and 20 mg) of a new angiotensin I-converting enzyme inhibitor, imidapril, on a) systemic hemodynamics (arterial pressure, heart rate, cardiac output), b) brachial and common carotid arteries' hemodynamics (diameter and blood flow, pulsed Doppler technique), c) cerebral hemody...
journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1472-8206.1994.tb00783.x
更新日期:1994-01-01 00:00:00
abstract::Lithium causes erectile dysfunction in patients but its mechanism is yet unknown. The aim of our study was to verify the effect of acute lithium administration on the nonadrenergic noncholinergic (NANC)- and endothelium-mediated relaxation of guinea pig isolated corpus cavernosum. Although lithium (0.5, 1, and 5mm) ha...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2010.00825.x
更新日期:2011-04-01 00:00:00
abstract::There is now substantial data in the literature showing that statins can protect against cerebral ischemia. This neuroprotective potency is related to their pleiotropic effects that modulate various pathways implicated in the pathophysiology of stroke. It has been demonstrated that statins exert anti-inflammatory and ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12035
更新日期:2014-06-01 00:00:00
abstract::Research in the last two decades has unveiled an important role for neuroinflammation in the degeneration of the nigrostriatal dopaminergic (DA) pathway that constitutes the pathological basis of the prevailing movement disorder, Parkinson's disease (PD). Neuroinflammation is characterized by the activation of brain g...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2008.00616.x
更新日期:2008-10-01 00:00:00
abstract::Despite the benefits of chrysotherapy the responsible mechanism of action of gold compounds remains unclear. At a concentration of 5 x 10(-4) M, sodium aurothiopropanol sulfonate (SAS) modified the in vitro proliferation kinetics of articular chondrocytes by reducing growth, viability and plating efficiency. Flow cyto...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1988.tb00621.x
更新日期:1988-01-01 00:00:00
abstract::Heart transplant is considered to be an extremely severe ischemia-reperfusion sequence. Post-ischemic dysfunction triggers multiple processes especially oxidative stress, but the mechanisms remain unclear. Free radical interactions lead to peroxynitrite generation, which seems to be involved in early post-transplant h...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2007.00467.x
更新日期:2007-04-01 00:00:00
abstract::The airway epithelium is composed of a heterogeneous population of cells. This epithelial layer is not only a physical barrier but also a target responding to a variety of inflammatory mediators. These cells can respond by releasing contracting and relaxing factors to modulate airway responsiveness. They can also meta...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.1993.tb00240.x
更新日期:1993-01-01 00:00:00
abstract::In this review, the major enzyme systems involved in vivo in the oxidative metabolism of xenobiotic amines in humans are discussed, i.e. the monooxygenases [cytochrome P450 system (CYPs) and flavin-containing monooxygenases (FMOs)] and the amine oxidases (AOs). Concerning the metabolism of xenobiotic amines (drugs in ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2007.00498.x
更新日期:2007-10-01 00:00:00
abstract::We have previously shown that kaolinite slowed down gastric emptying and intestinal transit and induced changes in enteric mechanical activities. As gastric emptying and intestinal transit have been shown to be regulated by nitric oxide (NO), the effect of an imposed ingestion of kaolinite on enteric nitrergic innerva...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12040
更新日期:2014-08-01 00:00:00
abstract::A survey was run on a sample of 134 French GPs from the Rhône-Alpes region, in an attempt to investigate the way they recollect important clinical trials that should have an impact on their practice. It was found that 1) most of them did not remember these trials (however, the awareness score did vary throughout the t...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1991.tb00721.x
更新日期:1991-01-01 00:00:00