Abstract:
:In vitro preparations of rabbit heart were made from which measurements of effective refractory period (ERP), atrio-Hisian (A-H) and His-Purkinje (H-P) conduction times could be obtained, analogous to electrophysiological measurements customarily carried out in vivo. Intracellular potentials also were recorded from the sino-atrial (SA) node, atrium, bundle of His, preterminal Purkinje fibres and papillary muscles. The effects of a range of concentrations of three new antiarrhythmic drugs, melperone, cibenzoline and alinidine were compared, the lower concentrations studied corresponding to clinical levels. At low concentrations the effects of melperone, inducing bradycardia and lengthening ERP, could be attributed to prolongation of action potential duration (APD) in the sinus node and atrial and ventricular tissues. The slope of slow diastolic depolarization was not altered, nor was there any change in A-H or H-P conduction time, or in maximum rate of depolarization (MRD). At higher concentrations melperone had a substantial class 1 action, but there was no negative inotropic effect, or other evidence of restriction of slow inward current. Cibenzoline was primarily a class 1 agent but also lengthened APD to some extent in the SA node and in atrial and ventricular muscle, but not in Purkinje fibres. APD thus became more uniform along the ventricular conducting pathway. Cibenzoline also depressed contractions and increased A-H conduction time, implying restriction of slow inward current. The bradycardia could thus be attributed to a slowing of both depolarization and repolarization in the SA node, without any change in slope of the slow diastolic depolarization. Conduction time was increased in all tissues. 8 Alinidine greatly reduced the slope of the slow diastolic depolarization and slightly lengthened APD in the SA node. MRD was also reduced in the SA node, and A-H conduction time was increased, implying some restriction of slow inward current. However, there was no negative inotropic effect. 9 Alinidine had no significant effect on MRD in atrium, ventricle or Purkinje cells, nor was H-P conduction time altered, implying absence of effect on fast inward current. APD was moderately lengthened in atrium and ventricle but not in Purkinje cells. 10 It was concluded that the effects of the drugs in the sinus node and on ERP and on A-H and H-P conduction times could be accounted for by their selective cellular actions in different regions of the heart.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Millar JS,Vaughan Williams EMdoi
10.1111/j.1476-5381.1983.tb10007.xsubject
Has Abstractpub_date
1983-07-01 00:00:00pages
701-9issue
3eissn
0007-1188issn
1476-5381journal_volume
79pub_type
杂志文章abstract::Low concentrations of several emetic, purgative or irritant drugs in the absence of added co-factors stimulated conversion of arachidonic acid to prostaglandin E2 and F2alpha by prostaglandin synthetase extracted from bull seminal vesicles (BSV prostaglandin synthetase). Their effect was dependent on concentration and...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb10396.x
更新日期:1976-10-01 00:00:00
abstract::1. Previous work from our laboratory has shown that cannabis induces aggressive behaviour in rats that have been deprived of rapid eye movement (REM) sleep. It was suggested that this effect was related to brain catecholamines, with dopamine playing an agonist role and noradrenaline an inhibitory one. The present pape...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08429.x
更新日期:1977-11-01 00:00:00
abstract::1. We examined how gamma-aminobutyric acid (GABA) influences interaction of picrotoxin and tert-butylbicyclophosphorothionate (TBPS) with recombinant rat alpha 1 beta 2 gamma 2 GABAA receptors stably expressed in human embryonic kidney cells (HEK293), as monitored with changes in Cl- currents measured by the whole-cel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16368.x
更新日期:1995-06-01 00:00:00
abstract::1. Peroxynitrite, a potent cytotoxic oxidant formed by the reaction of nitric oxide with superoxide anion, and hydroxyl radical, formed in the iron-catalysed Fenton reaction, are important mediators of reperfusion injury. In in vitro studies, DNA single strand breakage, triggered by peroxynitrite or by hydroxyl radica...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701234
更新日期:1997-07-01 00:00:00
abstract::1. A crude preparation of toxin was extracted from a sample of mussels Mytilus edulis, part of a batch responsible for many cases of paralytic shellfish poisoning.2. The crude extract was partially purified by absorption on sodium Amberlite ion-exchange resin. Two toxins were recovered by elution from the Amberlite, a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb10660.x
更新日期:1970-12-01 00:00:00
abstract::1 N-2-Chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long-term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb08619.x
更新日期:1976-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12690
更新日期:2014-07-01 00:00:00
abstract::1. 5-Hydroxytryptamine (5-HT) transport has been investigated in rat blood platelets poisoned with dinitrophenol-sodium fluoride or ouabain.2. The inhibition of transport produced by different concentrations of the metabolic inhibitors has been correlated with changes in the internal Na(+) and K(+) concentrations of t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07220.x
更新日期:1971-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:High resting heart rate is a predictor for total and cardiovascular mortality independent of other risk factors in patients with coronary artery disease. We tested the hypothesis that a reduction of resting heart rate with the cardiac pacemaker I(f) current inhibitor ivabradine prevents the endot...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.116
更新日期:2008-06-01 00:00:00
abstract::1. The present study addressed the role of neuropeptide (NPY) Y2 receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Wester...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706774
更新日期:2006-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:5-HT receptor agonists have variable nociceptive effects within the spinal cord. While there is some evidence for 5-HT(1A) spinally-mediated analgesia, the role of other 5-HT(1) receptor subtypes remains unclear. In the present study, we examined the spinal actions of a range of 5-HT(1) agonists,...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01685.x
更新日期:2012-03-01 00:00:00
abstract::1. The calcium sensitivity of force production of cardiac muscle fibres is altered by certain drugs. The sites of action of three such compounds (pimobendan, sulmazole, isomazole) within the myofibril have been investigated. Calmodulin antagonists, perhexilene and bepridil, which have been shown to alter the calcium d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14092.x
更新日期:1990-08-01 00:00:00
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-lif...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703337
更新日期:2000-05-01 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::Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonar...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15248
更新日期:2020-09-01 00:00:00
abstract::1 The effects of 4-Chloro-m-Cresol (4-CmC) were examined on heterologously expressed wild type (WT), Paramyotonia Congenita (R1448H) and Hyperkalemic Periodic Paralysis (M1360V) mutant alpha-subunits of human muscle sodium channels. 2 Block of rested sodium channels caused by 4-CmC was concentration-dependent with an ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702896
更新日期:1999-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The passage of drugs across the blood-brain barrier (BBB) limits the efficacy of chemotherapy in brain tumours. For instance, the anticancer drug doxorubicin, which is effective against glioblastoma in vitro, has poor efficacy in vivo, because it is extruded by P-glycoprotein (Pgp/ABCB1), multidr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02103.x
更新日期:2012-12-01 00:00:00
abstract::1. The effects of the intravenous injection of Kö 1173, a new anticonvulsant drug, phenytoin and procainamide were studied on three types of cardiac arrhythmia in dogs.2. Ventricular ectopic beats produced by intravenous injection of adrenaline in anaesthetized dogs respired with halothane were abolished by Kö 1173, 0...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb08114.x
更新日期:1972-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:JNJ-Q2, a novel broad-spectrum fluoroquinolone with anti-methicillin-resistant Staphylococcus aureus activity, was evaluated in a comprehensive set of non-clinical and clinical cardiovascular safety studies. The effect of JNJ-Q2 on different cardiovascular parameters was compared with that of mox...
journal_title:British journal of pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1476-5381.2012.01874.x
更新日期:2012-07-01 00:00:00
abstract::The release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) from the strips of guinea-pig ileum was investigated in the presence of neurotensin. Neurotensin evoked the release of [3H]-GABA from the strips preloaded with [3H]-GABA, and the evoked release was Ca2+-dependent and tetrodotoxin-sensitive. Hexameth...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11204.x
更新日期:1987-03-01 00:00:00
abstract::1. This study examined the impact of allopurinol on the renal functional responses to a 30 min period of ischaemia in anaesthetized rats. 2. Immediately on reperfusion, blood pressure rose transiently, while renal blood flow remained stable throughout at control values. Glomerular filtration rate was decreased by some...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702789
更新日期:1999-09-01 00:00:00
abstract::Anthracyclines can cause cumulative dose-related cardiotoxicity characterized by changes in Ca(2+) metabolism, including dysfunction of the sacroplasmic reticulum (SR) and decreased expression of Ca(2+)-handling proteins, such as the ryanodine receptor (RyR2). In this study, we examined the effect of dexrazoxane (ICRF...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703538
更新日期:2000-09-01 00:00:00
abstract::Free radicals as well as the AT1 receptor are involved in the pathogenesis of cardiovascular disease. Both the intracellular mechanisms of AT1 receptor regulation and the effect of free radicals on AT1 receptor expression are currently unknown. This study investigates the role of free radicals in the modulation of AT1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703623
更新日期:2000-10-01 00:00:00
abstract::1. Hypercholesterolaemia often occurs in patients with type 2 diabetes, who therefore encounter administration of HMG-CoA reductase inhibitors. Alteration of pancreatic beta-cell function leading to an impaired insulin secretory response to glucose plays a crucial role in the pathogenesis of type 2 diabetes. Therefore...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702397
更新日期:1999-03-01 00:00:00
abstract::1. Exposure of isolated skeletal muscle to troglitazone has resulted in inconsistent findings ranging from inhibition to stimulation of fuel oxidation and the glycogenic pathway. To better understand such variation in outcome, the present study used isolated rat soleus muscle strips to examine the interdependent influ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705162
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Post-operative ileus (POI) is induced by intestinal inflammation. Here, we aimed to clarify the effects of 5-HT3 receptor antagonists against POI. EXPERIMENTAL APPROACH:We administered three 5-HT3 receptor antagonists, ondansetron, tropisetron and palonosetron, to a mouse model of POI induced by...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13006
更新日期:2015-02-01 00:00:00
abstract::1. Effects of phorbol esters on the cytosolic Ca2+ level ([Ca2+]i) and muscle tension in the intestinal smooth muscle of guinea-pig taenia caeci were examined. 2. 12-Deoxyphorbol 13-isobutyrate (DPB, 1 microM) did not change the [Ca2+]i and tension in resting muscle. 3. In high K(+)-stimulated muscle, 1 microM DPB tra...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13558.x
更新日期:1993-05-01 00:00:00
abstract::1. The present study was designed to evaluate the nature of intervening agents in L-DOPA- and dopamine-induced neurotoxicity in Neuro-2A cells. 2. In the absence of cells and in conditions of light protection, at 37 degrees C, L-DOPA or dopamine (1 mM) in culture medium degraded spontaneously in a time-dependent manne...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704982
更新日期:2002-12-01 00:00:00
abstract::It was confirmed that morphine administration in vivo produced a selective decrease in the calcium content of synaptosomal fractions prepared from rat cerebral cortices. This effect was prevented by naloxone. 2 After morphine or naloxone, there were no changes in the sodium, potassium and magnesium contents of any of ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb10379.x
更新日期:1976-08-01 00:00:00
abstract::For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threat...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1111/j.1476-5381.2010.00964.x
更新日期:2010-11-01 00:00:00