No proarrhythmic properties of the antibiotics Moxifloxacin or Azithromycin in anaesthetized dogs with chronic-AV block.

Abstract:

BACKGROUND & PURPOSE:The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has not been shown to cause torsades de pointes arrhythmias (TdP). Azithromycin is a macrolide antibiotic that has rarely been associated, clinically, with cases of proarrhythmia. As there is a lack of clinical data available, the cardiac safety of these drugs was assessed in a TdP-susceptible animal model by evaluating their repolarization and proarrhythmia effects. EXPERIMENTAL APPROACH & KEY RESULTS:In transfected HEK cells, the IC(50)s for I (hERG) were 45+/-6 and 856+/-259 microg ml(-1) for moxifloxacin and azithromycin, respectively. Intravenous administration of 2 and 8 mg kg(-1) moxifloxacin (total peak-plasma concentrations 4.6+/-1.5 and 22.9+/-6.8 microg ml(-1)) prolonged the QT(c) in 6 anaesthetized dogs with chronic AV block by 7+/-3 and 21+/-19%, respectively. Similar intravenous doses of azithromycin (total peak-plasma concentrations 5.4+/-1.3 and 20.8+/-4.9 microg ml(-1)) had no electrophysiological effects in the same dogs. The reference compound, dofetilide (25 microg kg(-1) i.v.) caused QT(c) prolongation (29+/-15%) and TdP in all dogs. Beat-to-beat variability of repolarization (BVR), quantified as short-term variability of the left ventricular monophasic action potential duration, was only increased after dofetilide (1.8+/-0.7 to 3.8+/-1.5 ms; P<0.05). CONCLUSION & IMPLICATIONS:As neither moxifloxacin nor azithromycin caused TdP or an increase in the BVR, we conclude that both drugs can be used safely in clinical situations.

journal_name

Br J Pharmacol

authors

Thomsen MB,Beekman JD,Attevelt NJ,Takahara A,Sugiyama A,Chiba K,Vos MA

doi

10.1038/sj.bjp.0706900

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

1039-48

issue

8

eissn

0007-1188

issn

1476-5381

pii

0706900

journal_volume

149

pub_type

杂志文章
  • The peptide Phα1β, from spider venom, acts as a TRPA1 channel antagonist with antinociceptive effects in mice.

    abstract:BACKGROUND AND PURPOSE:Peptides from venomous animals have long been important for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide from the venom of the armed spider Phoneutria nigriventer, produces analgesia by blocking the TRPA1 channel. EXPERIMENTA...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13652

    authors: Tonello R,Fusi C,Materazzi S,Marone IM,De Logu F,Benemei S,Gonçalves MC,Coppi E,Castro-Junior CJ,Gomez MV,Geppetti P,Ferreira J,Nassini R

    更新日期:2017-01-01 00:00:00

  • Endothelium-dependent hyperpolarization of canine coronary smooth muscle.

    abstract::1. Experiments were designed to determine whether endothelium-dependent relaxing factor(s) released by acetylcholine from the canine femoral artery influences the membrane potential of coronary arterial smooth muscle. 2. The membrane potential was recorded in small canine coronary arteries (internal diameter less than...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1988.tb10306.x

    authors: Feletou M,Vanhoutte PM

    更新日期:1988-03-01 00:00:00

  • Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid.

    abstract::1. TRPM2 is a Ca2+ -permeable nonselective cation channel activated by intracellular ADP-ribose (ADPR) and by hydrogen peroxide (H2O2). We investigated the modulation of TRPM2 activity by N-(p-amylcinnamoyl)anthranilic acid (ACA). ACA has previously been reported to inhibit phospholipase A2 (PLA2). 2. Using patch-clam...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706739

    authors: Kraft R,Grimm C,Frenzel H,Harteneck C

    更新日期:2006-06-01 00:00:00

  • Ischaemia/reperfusion selectively attenuates coronary vasodilatation to an adenosine A2- but not to an A1-agonist in the dog.

    abstract::1. The effects of myocardial ischaemia/reperfusion were tested on the coronary vasorelaxant responses to agonists selective for the A1 and A2 adenosine receptor subtypes in the dog. The left anterior descending (LAD) coronary artery was occluded distal to the first diagonal branch. The occlusion was maintained for 1 h...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1994.tb14877.x

    authors: Cox BF,Greenland BD,Perrone MH,Merkel LA

    更新日期:1994-04-01 00:00:00

  • Responses of rabbit portal vein to histamine.

    abstract::1 Histamine produced a dose-dependent contraction of the isolated portal vein of the rabbit. This contraction was not antagonized by atropine, methysergide, indomethacin, cocaine or 6-hydroxy-dopamine, nor by pretreatment of the rabbit with reserpine. 2 The response to histamine was blocked by H1-receptor antagonists ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1978.tb08441.x

    authors: Cook DA,Macleod KM

    更新日期:1978-02-01 00:00:00

  • Therapeutic potential of histamine H₄ receptor agonists in triple-negative human breast cancer experimental model.

    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

    authors: Martinel Lamas DJ,Croci M,Carabajal E,Crescenti EJ,Sambuco L,Massari NA,Bergoc RM,Rivera ES,Medina VA

    更新日期:2013-09-01 00:00:00

  • Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries.

    abstract:BACKGROUND AND PURPOSE:Calcitonin gene-related peptide (CGRP) is a potent vasodilator, implicated in the pathogenesis of migraine. CGRP activates a receptor complex comprising, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). In vitro studies indicate recycling of CLR●RAMP1 is ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2012.02129.x

    authors: McNeish AJ,Roux BT,Aylett SB,Van Den Brink AM,Cottrell GS

    更新日期:2012-12-01 00:00:00

  • Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat.

    abstract:BACKGROUND AND PURPOSE:Recent findings suggest that the noxious gas H(2)S is produced endogenously, and that physiological concentrations of H(2)S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H(2)S to modulate carrageenan-induced sy...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2010.00640.x

    authors: Ekundi-Valentim E,Santos KT,Camargo EA,Denadai-Souza A,Teixeira SA,Zanoni CI,Grant AD,Wallace J,Muscará MN,Costa SK

    更新日期:2010-04-01 00:00:00

  • Study of the effector mechanism involved in the production of haemorrhagic necrosis of the small intestine in rat passive anaphylaxis.

    abstract::1. The effector mechanism of intestinal necrosis in rat anaphylaxis was studied following several complementary approaches: (i) the use of monoclonal antibodies (mAb) belonging to different classes (IgG1, IgG2b and IgE anti-DNP), (ii) the assay of mediators, and (iii) the use of pharmacological tools. 2. Lethality and...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1994.tb13197.x

    authors: Pellón MI,Steil AA,Furió V,Sánchez Crespo M

    更新日期:1994-08-01 00:00:00

  • Brain serotoninergic nervous system is involved in bombesin-induced frequent urination through brain 5-HT7 receptors in rats.

    abstract:BACKGROUND AND PURPOSE:Psychological stress exacerbates symptoms of urinary bladder dysfunction; however, the underlying brain mechanisms are unclear. We have demonstrated that centrally administered bombesin, a stress-related neuropeptide, facilitates the rat micturition reflex. Brain bombesin-like peptides modulate t...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13941

    authors: Shimizu T,Shimizu S,Wada N,Takai S,Shimizu N,Higashi Y,Kadekawa K,Majima T,Saito M,Yoshimura N

    更新日期:2017-09-01 00:00:00

  • The application of 'omics' to pulmonary arterial hypertension.

    abstract::Recent genome-wide analyses of rare and common sequence variations have brought greater clarity to the genetic architecture of pulmonary arterial hypertension and implicated novel genes in disease development. Transcriptional signatures have been reported in whole lung tissue, pulmonary vascular cells and peripheral c...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.15056

    authors: Harbaum L,Rhodes CJ,Otero-Núñez P,Wharton J,Wilkins MR

    更新日期:2021-01-01 00:00:00

  • Changes in plasma noradrenaline concentration as a measure of release rate.

    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

    authors: Benedict CR,Fillenz M,Stanford C

    更新日期:1978-10-01 00:00:00

  • Activation by calcium alone of chloride secretion in T84 epithelial cells.

    abstract::1. The goal of this study was to determine if an increase in cytoplasmic calcium concentration ([Ca2+]i), in the absence of additional second messengers derived from membrane phospholipid turnover, is a sufficient signal to induce chloride secretion across monolayers of the human colonic epithelial line, T84. 2. Thaps...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1993.tb13599.x

    authors: Kachintorn U,Vajanaphanich M,Traynor-Kaplan AE,Dharmsathaphorn K,Barrett KE

    更新日期:1993-06-01 00:00:00

  • Clotrimazole analogues: effective blockers of the slow afterhyperpolarization in cultured rat hippocampal pyramidal neurones.

    abstract::1. The pharmacology of the slow afterhyperpolarization (sAHP) was studied in cultured rat hippocampal pyramidal neurones. 2. Clotrimazole, its in vivo metabolite, 2-chlorophenyl-bisphenyl-methanol (CBM) and the novel analogues, UCL 1880 and UCL 2027, inhibited the sI(AHP) with similar IC50s (1-2 microM). 3. Clotrimazo...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703895

    authors: Shah MM,Miscony Z,Javadzadeh-Tabatabaie M,Ganellin CR,Haylett DG

    更新日期:2001-02-01 00:00:00

  • EP1- and FP-mediated cross-desensitization of the alpha (alpha) and beta (beta) isoforms of the human thromboxane A2 receptor.

    abstract::1. Heterologous desensitization or intermolecular cross-talk plays a critical role in regulating intracellular signalling by diverse members of the G-protein-coupled receptor superfamily. We have previously established that the alpha and beta isoforms of the human thromboxane A(2) receptor (TP) undergo differential de...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705695

    authors: Kelley-Hickie LP,Kinsella BT

    更新日期:2004-05-01 00:00:00

  • Passage of intravenously administered tubocurarine into the liquor space in man and dog.

    abstract::1. In anaesthetized patients under controlled respiration, samples of lumbar cerebrospinal fluid were withdrawn 15 and 60 min after an intravenous injection of 30 mg tubocurarine. When tested on the frog rectus muscle preparation contracted by acetylcholine, they exerted curare-like activity which corresponded to betw...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1973.tb08206.x

    authors: Devasankaraiah G,Haranath PS,Krishnamurty A

    更新日期:1973-04-01 00:00:00

  • Dual role of nitrergic neurotransmission in the bed nucleus of the stria terminalis in controlling cardiovascular responses to emotional stress in rats.

    abstract:BACKGROUND AND PURPOSE:The aim of the present study was to assess the interaction of nitrergic neurotransmission within the bed nucleus of the stria terminalis (BNST) with local glutamatergic and noradrenergic neurotransmission in the control of cardiovascular responses to acute restraint stress in rats. EXPERIMENTAL ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.14447

    authors: Barretto-de-Souza L,Adami MB,Benini R,Crestani CC

    更新日期:2018-10-01 00:00:00

  • Inhibition of slow Ca(2+)-activated K(+) current by 4-aminopyridine in rat hippocampal CA1 pyramidal neurones.

    abstract::1. The effect of 4-aminopyridine (4-AP) on the slow afterhyperpolarization (sAHP) seen after high frequency dendritic or somatic firing was investigated in rat hippocampal CA1 pyramidal neurones (PC). Intracellular recordings were obtained from the distal apical dendrites and somata and suprathreshold depolarizing cur...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704533

    authors: Andreasen M

    更新日期:2002-02-01 00:00:00

  • A patch-clamp study of K(+)-channel activity in bovine isolated tracheal smooth muscle cells.

    abstract::1. Single smooth muscle cells were isolated from bovine trachealis by enzymic digestion. The properties of large conductance plasmalemmal K(+)-channels in these cells were studied by the patch-clamp recording technique. 2. Recordings were made from inside-out plasmalemmal patches when [K+] was symmetrically high (140 ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1991.tb12269.x

    authors: Green KA,Foster RW,Small RC

    更新日期:1991-04-01 00:00:00

  • Effect of 1-aminocyclopropanecarboxylic acid on N-methyl-D-aspartate-stimulated [3H]-noradrenaline release in rat hippocampal synaptosomes.

    abstract::1. The effect of 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex that exhibits neuroprotective, anxiolytic and antidepressant-like actions, was investigated in a functional assay for presynaptic NMDA receptors. 2. NMDA (100 microM) pr...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1996.tb15484.x

    authors: Clos MV,Garcia Sanz A,Trullas R,Badia A

    更新日期:1996-06-01 00:00:00

  • Preclinical evaluation of [18 F]MA3: a CB2 receptor agonist radiotracer for PET.

    abstract:BACKGROUND AND PURPOSE:Non-invasive in vivo imaging of cannabinoid CB2 receptors using PET is pursued to study neuroinflammation. The purpose of this study is to evaluate the in vivo binding specificity of [18 F]MA3, a CB2 receptor agonist, in a rat model with local overexpression of human (h) CB2 receptors. METHODS:[...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.14564

    authors: Attili B,Celen S,Ahamed M,Koole M,Haute CVD,Vanduffel W,Bormans G

    更新日期:2019-05-01 00:00:00

  • Effects of non-sedative anxiolytic drugs on responses to GABA and on diazepam-induced enhancement of these responses on mouse neurones in cell culture.

    abstract::1. Intracellular microelectrode recording techniques were performed on mouse spinal cord and cerebral hemisphere neurones grown in primary dissociated cell culture. The effects of several anxiolytics applied by local pressure ejection on responses to gamma-aminobutyric acid (GABA) evoked by iontophoresis were investig...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1988.tb16554.x

    authors: De Deyn PP,Macdonald RL

    更新日期:1988-09-01 00:00:00

  • Modulation of a recombinant invertebrate gamma-aminobutyric acid receptor-chloride channel complex by isoflurane: effects of a point mutation in the M2 domain.

    abstract::1. Inhalational anaesthetics modulate ligand-gated ion channels at clinical concentrations. In this paper we address submolecular mechanisms for gamma-aminobutyric acid (GABA) receptor modulation by isoflurane. 2. Wild-type Drosophila melanogaster homo-oligomeric GABA receptors were characterized and compared with an ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701417

    authors: Edwards MD,Lees G

    更新日期:1997-10-01 00:00:00

  • Effects of changes in the structure of enkephalins and of narcotic analgesic drugs on their interactions with mu- and delta-receptors.

    abstract::1 The activity pattern of analogues of the enkephalins was determined in four parallel assays, the inhibition of the electrically evoked contraction of the guinea-pig ileum and mouse vas deferens at 36 degrees C and the inhibition of [(3)H]-naltrexone and [(3)H]-leucine-enkephalin binding at 0 to 4 degrees C in homoge...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1980.tb10422.x

    authors: Kosterlitz HW,Lord JA,Paterson SJ,Waterfield AA

    更新日期:1980-02-01 00:00:00

  • Heterogeneity in the mechanisms of vasorelaxation to anandamide in resistance and conduit rat mesenteric arteries.

    abstract::1 In order to address mechanistic differences between arterial vessel types, we have compared the vasorelaxant actions of anandamide in resistance (G3) and conduit (G0) mesenteric arteries. 2 Anandamide produced concentration-dependent relaxations of pre-constricted G3 arteries with a maximal response that was signifi...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705810

    authors: O'Sullivan SE,Kendall DA,Randall MD

    更新日期:2004-06-01 00:00:00

  • Necessity of divalent cations for recovery from carbachol-induced nicotinic acetylcholine receptor inactivation at snake twitch fibre endplates.

    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

    authors: Hardwick JC,Parsons RL

    更新日期:1993-10-01 00:00:00

  • The relaxant properties of human calcitonin gene-related peptide on vascular and extravascular capsular) smooth muscle of the isolated blood-perfused spleen of the anaesthetized dog.

    abstract::1. The 37 amino acid human calcitonin gene-related peptide (CGRP), was injected intra-arterially into the isolated, blood perfused spleen of the dog. 2. The only vascular response observed to CGRP, once threshold had been reached (10-20 fmol), was a dose-dependent splenic arterial vasodilatation. 3. The mean intra-art...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1989.tb11890.x

    authors: Withrington PG

    更新日期:1989-04-01 00:00:00

  • Analysis of the pharmacokinetic/pharmacodynamic relationship of a small molecule CXCR3 antagonist, NBI-74330, using a murine CXCR3 internalization assay.

    abstract:BACKGROUND AND PURPOSE:Pharmacokinetic/pharmacodynamic (PK/PD) models are necessary to relate the degree of drug exposure in vivo to target blockade and pharmacological efficacy. This manuscript describes a murine agonist-induced CXCR3 receptor internalization assay and demonstrates its utility for PK/PD analyses. EXP...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0707519

    authors: Jopling LA,Watt GF,Fisher S,Birch H,Coggon S,Christie MI

    更新日期:2007-12-01 00:00:00

  • Antagonism of the platelet activating factor-induced rise of the intracellular calcium ion concentration of U937 cells.

    abstract::1. U937 cells are a continuous line of human cells of committed monocytic origin which serve as a useful model for studying human monocytic function. The present study investigated the effect of platelet-activating factor (Paf) on intracellular free calcium ion concentration ([Ca2+]i) in U937 cells using the calcium f...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1988.tb11461.x

    authors: Ward SG,Westwick J

    更新日期:1988-04-01 00:00:00

  • Gallium modulates osteoclastic bone resorption in vitro without affecting osteoblasts.

    abstract:BACKGROUND AND PURPOSE:Gallium (Ga) has been shown to be effective in the treatment of disorders associated with accelerated bone loss, including cancer-related hypercalcemia and Paget's disease. These clinical applications suggest that Ga could reduce bone resorption. However, few studies have studied the effects of G...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2010.00665.x

    authors: Verron E,Masson M,Khoshniat S,Duplomb L,Wittrant Y,Baud'huin M,Badran Z,Bujoli B,Janvier P,Scimeca JC,Bouler JM,Guicheux J

    更新日期:2010-04-01 00:00:00