Abstract：
:Using a rat model which allows serial blood sampling and concurrent brain microdialysis sampling, we have investigated the temporal kinetic inter-relationship of levetiracetam in serum and brain extracellular fluid (frontal cortex and hippocampus) following systemic administration of levetiracetam, a new antiepileptic drug. Concurrent extracellular amino acid concentrations were also determined. After administration (40 or 80 mg kg(-1)), levetiracetam rapidly appeared in both serum (T(max), 0.4 - 0.7 h) and extracellular fluid (T(max), 2.0 - 2.5 h) and concentrations rose linearly and dose-dependently, suggesting that transport across the blood-brain barrier is rapid and not rate-limiting. The serum free fraction (free/total serum concentration ratio; mean+/-s.e.mean range 0.93 - 1.05) was independent of concentration and confirms that levetiracetam is not bound to blood proteins. The kinetic profiles for the hippocampus and frontal cortex were indistinguishable suggesting that levetiracetam distribution in the brain is not brain region specific. However, t(1/2) values were significantly larger than those for serum (mean range, 3.0 - 3.3 h vs 2.1 - 2.3 h) and concentrations did not attain equilibrium with respect to serum. Levetiracetam (80 mg kg(-1)) was associated with a significant reduction in taurine in the hippocampus and frontal cortex. Other amino acids were unaffected by levetiracetam. Levetiracetam readily and rapidly enters the brain without regional specificity. Its prolonged efflux from and slow equilibration within the brain may explain, in part, its long duration of action. The concurrent changes in taurine may contribute to its mechanism of action.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Tong X,Patsalos PNdoi
10.1038/sj.bjp.0704141subject
Has Abstractpub_date
2001-07-01 00:00:00pages
867-74issue
6eissn
0007-1188issn
1476-5381journal_volume
133pub_type
杂志文章abstract：:1. We studied the biochemical and contractile responses of isolated human myocardial tissue expressing native receptor variants of the 389G>R beta(1)-adrenoceptor polymorphism. 2. Right atrial appendage was obtained from homozygous RR patients (n=37) and homozygous GG patients (n=17) undergoing elective cardiac surger...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705030
更新日期：2003-01-01 00:00:00
abstract：:1. Acetylcholine mustard (N-2-chloroethyl-N-methyl-2-acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea-pig small intesting, as shown by the inhibition of the binding of E13-H]-propylbenzilycholine mustard ([3-H-PrBCM), an aff...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07372.x
更新日期：1975-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Dipyridamole enhances post-occlusive reactive hyperaemia (PORH) in the human forearm vascular bed. We hypothesize that this effect is completely mediated by increased adenosine receptor stimulation. To test this hypothesis, the effect of caffeine (an adenosine receptor antagonist) on dipyridamole...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.10
更新日期：2008-03-01 00:00:00
abstract：:In recent years there has been a growing recognition of the influence of sex on brain structure and function, and in relation, on the susceptibility, prevalence and response to treatment of psychiatric disorders. Most theories and descriptions of the effects of sex on the brain are dominated by an analogy to the curre...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12732
更新日期：2014-10-01 00:00:00
abstract：:1. In circular muscle strips of the fundus and corpus of guinea-pig stomach, mechanical responses to catecholamines were studied mainly in the presence of a prostaglandin biosynthesis inhibitor, meclofenamate. 2. Normal preparations developed considerable muscle tone, and adrenaline (10-100 microM) in the presence of ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14162.x
更新日期：1990-12-01 00:00:00
abstract：:1. The aim of this study was to investigate the cardiovascular effects of a novel, potent and specific phosphodiesterase 5 (PDE 5) inhibitor, 1,3 dimethyl-6-(2-propoxy-5-methane sulphonylamidophenyl)-pyrazolo[3,4-d]pyrimidin-4-(5H)-one (DMPPO) in phenylephrine-precontracted rat aortic rings and different in vivo rat p...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15548.x
更新日期：1996-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Methylene blue (MB) is commonly employed as a treatment for methaemoglobinaemia, malaria and vasoplegic shock. An increasing number of studies indicate that MB can cause 5-HT toxicity when administered with a 5-HT reuptake inhibitor. MB is a potent inhibitor of monoamine oxidases, but other targe...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01462.x
更新日期：2012-05-01 00:00:00
abstract：:1. In order to characterize the neuropeptide Y (NPY) Y1 receptors known to be present in rabbit isolated vas deferens and saphenous vein, the pharmacological activity of the selective NPY Y1 receptor agonists, [Leu31,Pro34] NPY and various other peptide agonists, together with the putative NPY antagonist, benextramine...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16311.x
更新日期：1995-05-01 00:00:00
abstract：:The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled through the concerted interactions of concentration-limited pathway components and a wide range of...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14038
更新日期：2017-12-01 00:00:00
abstract：:Peroxynitrite, a potent oxidant formed by the reaction of nitric oxide and superoxide causes thymocyte necrosis, in part, via activation of the nuclear enzyme poly(ADP-ribose) synthetase (PARS). The cytotoxic PARS pathway initiated by DNA strand breaks and excessive PARS activation has been shown to deplete cellular e...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702332
更新日期：1999-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The presence of the histamine H₄ receptor (H₄R) was previously reported in benign and malignant lesions and cell lines derived from the human mammary gland. The aim of this work was to evaluate the effects of H₄R ligands on the survival, tumour growth rate and metastatic capacity of breast cancer...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12137
更新日期：2013-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Endogenous cannabinoids (endocannabinoids) in the periaqueductal grey (PAG) play a vital role in mediating stress-induced analgesia. This analgesic effect of endocannabinoids is enhanced by pharmacological inhibition of their degradative enzymes. However, the specific effects of endocannabinoids ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12839
更新日期：2014-12-01 00:00:00
abstract：:The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1-yl)propyl]-5-ph...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb11138.x
更新日期：1986-09-01 00:00:00
abstract：:1. We have studied the transcellular biosynthesis of bioactive leukotrienes (LTs), generated upon blood cell-vascular wall interactions and their functional consequences, in the spontaneously beating, cell-perfused, heart of the rabbit. Rabbit isolated hearts were perfused under recirculating conditions (50 ml) with 5...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13943.x
更新日期：1993-11-01 00:00:00
abstract：:The interaction between nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) was investigated in isolated circular smooth muscle cells and strips of the guinea-pig gastric fundus. VIP induced a concentration-dependent inhibition of carbachol-induced contraction in smooth muscle cells with a maximum at 10(-6) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703089
更新日期：2000-02-01 00:00:00
abstract：:1. We have investigated the effects of chlorpheniramine, atropine and capsaicin pretreatment on inhaled sodium metabisulphite (MBS)-induced airway microvascular leakage and bronchoconstriction in anaesthetized guinea-pigs in order to clarify the mechanisms involved in these responses. The effects of frusemide and nedo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb12771.x
更新日期：1992-10-01 00:00:00
abstract：:1. The ability of the putative, selective post-junctional alpha 2-adrenoceptor antagonist, SK&F 104078 to antagonize the effects of structurally-diverse agonists at pre-junctional alpha 2-adrenoceptors in the guinea-pig ileum and rat vas deferens in vitro and in the rat heart in vivo, and at post-junctional alpha 2-ad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12281.x
更新日期：1991-04-01 00:00:00
abstract：UNLABELLED:Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose and lipid metabolism, by exerting pro-apoptotic effects in pancreatic beta cells and by facilitating inflammation in pancre...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13226
更新日期：2016-04-01 00:00:00
abstract：:1 The actions of ethylenediamine (EDA) and structurally related compounds were investigated by microiontophoresis in Wistar rats. 2 EDA inhibited, via a bicuculline-sensitive mechanism, the spontaneous firing rate of all cortical and pallidal cells tested. 3 The results with the analogues suggest that two amine groups...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08761.x
更新日期：1982-01-01 00:00:00
abstract：:Following the discovery of the first effective antiviral compound (idoxuridine) in 1959, nucleoside analogues, especially acyclovir (ACV) for the treatment of herpesvirus infections, have dominated antiviral therapy for several decades. However, ACV and similar acyclic nucleosides suffer from low aqueous solubility an...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0706446
更新日期：2006-01-01 00:00:00
abstract：:We tested the hypothesis that combined use of trophic factors and caspase inhibitors increases brain resistance to ischaemia in mice. Intracerebroventricular administration of bFGF (>10 ng) 30 min after MCA occlusion decreased infarct size and neurological deficit in a dose-dependent manner following 2 h ischemia and ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704075
更新日期：2001-06-01 00:00:00
abstract：:1. We have investigated the cellular target of K(+) channel blockers responsible for the inhibition of the EDHF-mediated relaxation in the rat mesenteric artery by studying their effects on tension, smooth muscle cell (SMC) membrane potential and endothelial cell Ca(2+) signal ([Ca(2+)](endo)). 2. In arteries contract...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704348
更新日期：2001-11-01 00:00:00
abstract：:1. Intraplantar administration of the nitric oxide (NO) donor, sodium nitroprusside (SNP), induces hyperaemia in the rat paw skin, which is in part due to release of calcitonin gene-related peptide (CGRP) from afferent nerve fibres. The present study examined whether prostaglandins or other inflammatory mediators part...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15081.x
更新日期：1995-11-01 00:00:00
abstract：:1. Human formyl peptide-receptor-like-1 (FPRL-1) is a promiscuous G protein-coupled receptor (GPCR), and belongs to a chemoattractant receptor family protein. This receptor has been reported to interact with various host-derived peptides and lipids involved in inflammatory responses. We described here, a novel role fo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705592
更新日期：2004-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:There is increasing evidence that potassium channels are involved in the cardiovascular dysfunction of sepsis. This evidence was obtained after the systemic inflammation, cardiovascular dysfunction and organ damage had developed. Here we have studied the consequences of early interference with po...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01324.x
更新日期：2011-07-01 00:00:00
abstract：:1 A method is described for repeated sampling of plasma noradrenaline (NA) in freely moving rats. Na concentration does not change during the day or after adrenalectomy. 2 Exogenous NA has a half-life of 1.5 min; drugs which block neuronal and extra-neuronal uptake lengthen this to 6.3 min. 3 Swim-stress leads to a st...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb17305.x
更新日期：1978-10-01 00:00:00
abstract：:1. The effects of dimethothiazine have been studied on the response of afferent fibres from primary and secondary endings of muscle spindles in the soleus muscle of the decerebrate cat during stretching of the muscle under controlled conditions.2. Dimethothiazine in doses of 1 to 4 mg/kg intravenously reduced the disc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb10360.x
更新日期：1970-07-01 00:00:00
abstract：:1. In order to clarify the mechanism of Ca-dependent excitatory action of maitotoxin (MTX), the most potent marine toxin known, patch-clamp techniques were used to analyse electrophysiological effects of MTX on guinea-pig isolated cardiac myocytes. 2. The whole-cell recordings showed that MTX (0.3 ng ml-1) produced a ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11370.x
更新日期：1987-11-01 00:00:00
abstract：:1. We have investigated the effect of phorbol esters and the down-regulation of protein kinase C on contraction of guinea-pig ileum longitudinal smooth muscle to carbachol and high K+. 2. Phorbol 12,13-dibutyrate (PDBu) enhanced the phasic component and inhibited or enhanced, respectively, the tonic component of contr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb14607.x
更新日期：1989-11-01 00:00:00
abstract：:1 In the guinea-pig vas deferens, grayanotoxin I (G-I), a diterpenic toxin isolated from certain ericaceous plants caused rhythmic contractions which were dose-dependent (5 x 10(-5) M - 10(-3) M); these followed an initial transient contraction.2 The G-I (3 x 10(-4) M)-induced contraction was markedly inhibited or abo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb08806.x
更新日期：1983-03-01 00:00:00
