Abstract：
:We investigated the rate of penetration into and the intra-relationship between the serum, cerebrospinal fluid (CSF) and regional brain extracellular fluid (bECF) compartments following systemic administration of lamotrigine in rat. The serum pharmacokinetics were biphasic with an initial distribution phase, (half-life approximately 3 h), and then a prolonged elimination phase of over 30 h. The serum pharmacokinetics were linear over the range 10 - 40 mg kg(-1). Using direct sampling of CSF with concomitant serum sampling, the calculated penetration half-time into CSF was 0.42+/-0.15 h. At equilibrium, the CSF to total serum concentration ratio (0.61+/-0.02) was greater than the free to total serum concentration (0.39+/-0.01). Using in vivo recovery corrected microdialysis sampling in frontal cortex and hippocampus with concomitant serum sampling, the calculated penetration half-time of lamotrigine into bECF, 0.51+/-0.11 h, was similar to that for CSF and was not area or dose dependent. At equilibrium, the bECF to total serum concentration ratio (0.40+/-0.04) was similar to the free to total serum concentration (0.39+/-0.01), and did not differ between hippocampus and frontal cortex. The species specific serum kinetics can explain the prolonged action of lamotrigine in rat seizure models. Lamotrigine has a relatively slow penetration into both CSF and bECF compartments compared with antiepileptic drugs used in acute seizures. Furthermore, the free serum drug concentration is not the sole contributor to the CSF compartment, and the CSF concentration is an overestimate of the bECF concentration of lamotrigine.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Walker MC,Tong X,Perry H,Alavijeh MS,Patsalos PNdoi
10.1038/sj.bjp.0703337subject
Has Abstractpub_date
2000-05-01 00:00:00pages
242-8issue
2eissn
0007-1188issn
1476-5381journal_volume
130pub_type
杂志文章abstract：:1.--The small protein Bv8, isolated from the amphibian skin, belongs to a novel family of secreted proteins linked to several biological effects. We describe the expression of Bv8/prokineticins and their receptors in mouse macrophages, and characterize their proinflammatory activities. 2.--The rodent analogue of Bv8, ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706467
更新日期：2006-01-01 00:00:00
abstract：:We studied the effects of the novel Na(+)/Ca(2+) exchange inhibitor KB-R7943, 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate, on the native nicotinic receptors present at the bovine adrenal chromaffin cells, as well as on rat brain alpha(3)beta(4) and alpha(7) nicotinic acetylcholine receptors (A...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703519
更新日期：2000-08-01 00:00:00
abstract：:Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705641
更新日期：2004-02-01 00:00:00
abstract：:1. Acute moderate hypoxia modifies the catalytic activity and expression of certain isoenzymes of hepatic cytochrome P450 (P450). The aim of this study was to document whether hypoxia affects hepatic P450 directly or through the release of serum mediators. 2. Rabbits were subjected to a FiO(2) of 8% for 48 h, sacrific...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704933
更新日期：2002-11-01 00:00:00
abstract：:The nature of the neurohypophyseal peptide receptor in the anococcygeus muscles from male mice was investigated. The rank order of potency of naturally occurring peptides was oxytocin greater than Arg-vasotocin greater than Arg-vasopressin greater than Lys-vasopressin, which is similar to that found in the uterus and ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb09482.x
更新日期：1986-05-01 00:00:00
abstract：:1. Previous studies demonstrated that elevation of the extracellular calcium concentration during a prolonged exposure to a high concentration of carbachol reverses the staurosporine-induced decrease in the extent of endplate resensitization in voltage-clamped snake twitch fibres. The present studies were designed to ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13896.x
更新日期：1993-10-01 00:00:00
abstract：:1. The effects of varying H+ and other cation concentrations on phospholipase activity were investigated on two particulate fractions from human lung, corresponding to the mitochondrial and microsomal fractions. 2. Three 14C-labelled substrates, arachidonyl-phosphatidylcholine (PC), -phosphatidylethanolamine (PE) and ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb15826.x
更新日期：1990-07-01 00:00:00
abstract：:1. The effects of intracameral injections of prostaglandins E(1), E(2), F(1a), F(2a), and A(1) were studied on the intraocular pressure (IOP) of rabbits anaesthetized with urethane.2. With the exception of prostaglandin F(1a), all the prostaglandins studied were found to be capable of producing a large, sustained rise...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb09533.x
更新日期：1969-09-01 00:00:00
abstract：:1. The measurement of changes in spike generation and membrane resistance in the guinea-pig taenia coli, using the sucrose gap extracellular recording method, has been shown to be a useful way to demonstrate the intrinsic sympathomimetic activity of the beta adrenoceptor blocking agents.2. Pronethalol, INPEA, MJ 1999,...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb10332.x
更新日期：1970-01-01 00:00:00
abstract：:1. We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically stimulate corneal epithelial wound healing in vitro and in vivo. We wished to identify which portion of the amino acid sequence of substance P might be responsible for this synergism. 2. Corneal epithelial migration was...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702550
更新日期：1999-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Recombinant human erythropoietin (rHuEPO) is currently the mainstay of renal anaemia treatment. Recently, rHuEPO has been shown to provide pleiotrophic tissue protection in various pathological conditions. However, the benefits of rHuEPO beyond anaemia treatment are limited because it increases r...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.02123.x
更新日期：2013-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:An alteration in the communication between the innate and adaptive immune cells is a hallmark of ulcerative colitis (UC). Semaphorin-3E (SEMA3E), a secreted guidance protein, regulates various immune responses. EXPERIMENTAL APPROACH:We investigated the expression of SEMA3E in colonic biopsies of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14614
更新日期：2019-05-01 00:00:00
abstract：:1. A quaternary derivative of (-)-hyoscyamine, phenthonium (Phen) induced a concentration-dependent increase in the rate of spontaneous quantal release of acetylcholine (ACh) at the mammalian neuromuscular junction, as shown by intracellular recordings of the miniature endplate potentials (m.e.p.ps) in rat diaphragm m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb15825.x
更新日期：1990-07-01 00:00:00
abstract：:1. We studied the lactotroph cells of the rat by both in vivo and in vitro pharmacological techniques for the presence of D1-receptors. Both approaches revealed the presence of D2-receptor, stimulated by quinpirole (resulting in an inhibition of prolactin secretion) and blocked by domperidone. 2. Administration of fen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12354.x
更新日期：1991-08-01 00:00:00
abstract：:The concentration in rat striatum of the meta and para isomers of tyramine and alpha-methyltyramine, after the administration of (+)-amphetamine, alpha-methyl-p-tyrosine (AMPT) and alpha-methylphenylalanine (AMPA) has been determined using chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Twenty...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10035.x
更新日期：1983-10-01 00:00:00
abstract：:1. Desensitization of the myocardial beta-adrenergic signal transduction pathway is an important mechanism which is involved in the progression of hypertensive heart disease. The aim of the present study was to evaluate the differential effects of chronic pharmacotherapy with an angiotensin converting enzyme (ACE)-inh...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701615
更新日期：1998-02-01 00:00:00
abstract：:1. We have investigated the effects of the selective phosphodiesterase (PDE) type 4 inhibitor, rolipram (0.01-1 microM) on cytosolic Ca2+ fluxes in FMLP-activated human neutrophils, as well as on superoxide production by, and release of elastase from, these cells. 2. Cytosolic Ca2+ fluxes were measured by use of fura-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701849
更新日期：1998-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The P2X(7) receptor exhibits complex pharmacological properties. In this study, binding of a [(3)H]-labelled P2X(7) receptor antagonist to human P2X(7) receptors has been examined to further understand ligand interactions with this receptor. EXPERIMENTAL APPROACH:The P2X(7) receptor antagonist, ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707196
更新日期：2007-05-01 00:00:00
abstract：:1 The influence of dopamine receptor agonists on gastric acid secretion stimulated by thyrotropin-releasing hormone (TRH) was studied in the perfused stomach of anaesthetized rats. 2 Intraventricular TRH produced a dose-dependent stimulation of basal gastric acid secretion. 3 Pretreatment with apomorphine, bromocripti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10524.x
更新日期：1983-05-01 00:00:00
abstract：:1. In urethane-anaesthetized guinea-pigs, under spontaneous respiration, indomethacin (1 mg kg-1 i.v., 10-45 min) approximately doubled the bronchoconstrictor effect (increase in airways resistance, R(aw)) of equieffective doses of histamine and 5-hydroxytryptamine (5-HT), but not that of acetylcholine or leukotriene ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11556.x
更新日期：1988-06-01 00:00:00
abstract：:The phenanthrene-derivative 9-phenanthrol is a recently identified inhibitor of the transient receptor potential melastatin (TRPM) 4 channel, a Ca(2+) -activated non-selective cation channel whose mechanism of action remains to be determined. Subsequent studies performed on other ion channels confirm the specificity o...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12582
更新日期：2014-04-01 00:00:00
abstract：:1. The effectiveness of alpha 1- and alpha 2-adrenoceptor activation was compared at different levels of the saphenous and cephalic vein of the dog in vitro. 2. Helically cut strips were used to determine concentration-response curves to phenylephrine, noradrenaline, UK-14,304 (5-bromo-6-(imidazoline-2-ylamino)-quinox...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12719.x
更新日期：1990-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Tanshinol borneol ester (DBZ) is a novel synthetic compound derived from Dantonic® , a botanical drug approved in 26 countries outside the United States for angina pectoris and currently undergoing FDA Phase III clinical trial. Here, we investigated the angiogenic effects of (S)-DBZ and (R)-DBZ i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14714
更新日期：2019-09-01 00:00:00
abstract：:1. The goal of this study was to investigate the effects of the delayed pharmacological preconditioning produced by an adenosine A(1)-receptor agonist (A(1)-DPC) against ventricular arrhythmias induced by ischaemia and reperfusion, compared to those of ischaemia-induced delayed preconditioning (I-DPC). 2. Eighty-nine ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704407
更新日期：2001-12-01 00:00:00
abstract：:1. General anaesthetics disrupt normal cell receptivity and responsiveness while sparing vital respiratory processes. Ultimate elucidation of the molecular basis of general anaesthesia presumes the identification of one or more subcellular components with appropriate sensitivity to the entire array of anaesthetics. 2....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701006
更新日期：1997-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:In mammalian cells, the anti-parasitic drug ivermectin is known as a positive allosteric modulator of the ATP-activated ion channel P2X4 and is used to discriminate between P2X4- and P2X7-mediated cellular responses. In this paper we provide evidence that the reported isoform selectivity of iverm...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.01987.x
更新日期：2012-09-01 00:00:00
abstract：:1. Microvascular permeability in the mesentery and consequent leakage of protein into the peritoneum of spontaneously hypertensive rats (SHR) and normotensive rats (NTR) was measured in vivo by the extravasation of Evans blue dye. 2. In sensitized NTR, challenge with antigen produced extensive increases in dye extrava...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701875
更新日期：1998-06-01 00:00:00
abstract：:It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702541
更新日期：1999-05-01 00:00:00
abstract：:1. Unique among the phospholipids, phosphatidylserine depresses brain energy metabolism when injected intravenously into mice in the form of sonicated liposomes. The possibility that this effect results from a metabolic transformation of phosphatidylserine is examined in this paper. 2. A strong enhancement of the phos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb08708.x
更新日期：1979-12-01 00:00:00
abstract：:1. Vascular endothelial and smooth muscle cells generate nitric oxide (NO) via different nitric oxide synthase (NOS) isozymes. Activation of the endothelial constitutive NOS (ecNOS) contributes to the maintenance of cardiovascular homeostasis, whereas expression of the endotoxin- and cytokine-inducible pathway (iNOS) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15510.x
更新日期：1996-07-01 00:00:00
