当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties.

The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties.

Abstract：

:1. CS-747 is a novel antiplatelet agent that generates an active metabolite, R-99224, in vivo. CS-747 itself was totally inactive in vitro. This study examined in vivo pharmacological profiles of CS-747 after single oral administration to rats. 2. Orally administered CS-747 (0.3 - 10 mg kg(-1)) partially but significantly decreased [(3)H]-2-methylthio-ADP binding to rat platelets. CS-747 (3 mg kg(-1), p.o.) treatment neutralized ADP-induced decreases of cyclic AMP concentrations induced by prostaglandin E(1), suggesting that metabolites of CS-747 interfere with G(i)-linked P2T receptor. 3. CS-747 (0.3 and 3 mg kg(-1), p.o.) markedly inhibited ex vivo washed platelet aggregation in response to ADP but not to thrombin. CS-747 also exhibited a marked inhibition of ADP-induced ex vivo platelet aggregation in PRP with a rapid onset (<0.5 h) and long duration (>3 days) of action (ED(50) at 4 h=1.2 mg kg(-1)). 4. R-99224 (IC(50)=45 microM) inhibited in vitro PRP aggregation in a concentration-related manner. 5. CS-747 prevented thrombus formation in a dose-related manner with an ED(50) value of 0.68 mg kg(-1). CS-747 was more potent than clopidogrel (6.2 mg kg(-1)) and ticlopidine (>300 mg kg(-1)). 6. CS-747, clopidogrel, and ticlopidine prolonged the bleeding time. The order of potency of these agents in this activity was the same as that in antiaggregatory and antithrombotic activities. 7. These findings indicate that CS-747 is an orally active and a potent antiplatelet and antithrombotic agent with a rapid onset and long duration of action, and warrants clinical evaluations of the agent.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Sugidachi A,Asai F,Ogawa T,Inoue T,Koike H

doi

10.1038/sj.bjp.0703237

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

1439-46

issue

7

eissn

0007-1188

issn

1476-5381

journal_volume

129

pub_type

杂志文章

相关文献

BRITISH JOURNAL OF PHARMACOLOGY文献大全
  • 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

  • The ventral pallidum and relapse in alcohol seeking.

    abstract：:Alcohol-use disorders are chronically relapsing conditions characterized by cycles of use, abstinence and relapse. The ventral pallidum (VP) is a key node in the neural circuits controlling relapse to alcohol seeking and a key target of pharmacotherapies for relapse prevention. There has been a significant increase in...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1111/bph.15160

    authors： Prasad AA,McNally GP

    更新日期：2020-09-01 00:00:00

  • Effects of diltiazem on electrical responses evoked spontaneously or by electrical stimulation in the antrum smooth muscle cells of the guinea-pig stomach.

    abstract：:In circular smooth muscle cells of the guinea-pig stomach (antrum), diltiazem (10(-6)-10(-5)M) blocked the overshooting spike potential generated either spontaneously or by electrical stimulation in the presence of 2 mM tetraethylammonium chloride, but did not block the slow wave and the abortive spike potential. The ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1985.tb11100.x

    authors： Ishikawa S,Komori K,Nagao T,Suzuki H

    更新日期：1985-12-01 00:00:00

  • TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability.

    abstract：BACKGROUND AND PURPOSE:Chromosomal instability is not only a hallmark of cancer but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1, also known as TTK), which is essential for chromosome alignment and for the spindle asse...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.13782

    authors： Choi M,Min YH,Pyo J,Lee CW,Jang CY,Kim JE

    更新日期：2017-06-01 00:00:00

  • Effects of morphine, physostigmine and raphe nuclei stimulation on 5-hydroxytryptamine release from the cerebral cortex of the cat.

    abstract：:1. The release of 5-hydroxytryptamine (5-HT) from the cerebral cortex and caudate nucleus of brainstem-transected cats and from the cerebral cortex of rats anaesthetized with urethane was determined by radioenzymatic and biological assay. 2. The stimulation of nucleus linearis intermedius of raphe doubles the basal 5-...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1979.tb07863.x

    authors： Aiello-Malmberg P,Bartolini A,Bartolini R,Galli A

    更新日期：1979-04-01 00:00:00

  • Transparency in Research involving Animals: The Basel Declaration and new principles for reporting research in BJP manuscripts.

    abstract：:This article discusses the background to the need for change in the reporting of experiments involving animals, including a report of a consensus meeting organised by the Basel Declaration Society and Understanding Animal Research UK that sought to Internationalise guidelines for reporting experiments involving animal...

    journal_title：British journal of pharmacology

    pub_type： 社论

    doi：10.1111/bph.12956

    authors： McGrath JC,McLachlan EM,Zeller R

    更新日期：2015-05-01 00:00:00

  • Relief learning is dependent on NMDA receptor activation in the nucleus accumbens.

    abstract：BACKGROUND AND PURPOSE:Recently, we demonstrated that the nucleus accumbens (NAC) is required for the acquisition and expression of relief memory. The purpose of this study was to investigate the role of NMDA receptors within the NAC in relief learning. EXPERIMENTAL APPROACH:The NMDA receptor antagonist 2-amino-5-phos...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.13070

    authors： Mohammadi M,Fendt M

    更新日期：2015-05-01 00:00:00

  • 5-HT3 receptors promote colonic inflammation via activation of substance P/neurokinin-1 receptors in dextran sulphate sodium-induced murine colitis.

    abstract：BACKGROUND AND PURPOSE:5-HT (serotonin) regulates various physiological functions, both directly and via enteric neurons. The present study investigated the role of endogenous 5-HT and 5-HT3 receptors in the pathogenic mechanisms involved in colonic inflammation, especially in relation to substance P (SP) and the neuro...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.13482

    authors： Utsumi D,Matsumoto K,Amagase K,Horie S,Kato S

    更新日期：2016-06-01 00:00:00

  • Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo.

    abstract：BACKGROUND AND PURPOSE:We recently reported that AAV1-Rheb(S16H) transduction could protect hippocampal neurons through the induction of brain-derived neurotrophic factor (BDNF) in the rat hippocampus in vivo. It is still unclear how neuronal BDNF produced by AAV1-Rheb(S16H) transduction induces neuroprotective effects...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.14882

    authors： Jeon MT,Moon GJ,Kim S,Choi M,Oh YS,Kim DW,Kim HJ,Lee KJ,Choe Y,Ha CM,Jang IS,Nakamura M,McLean C,Chung WS,Shin WH,Lee SG,Kim SR

    更新日期：2020-02-01 00:00:00

  • Presynaptic alpha-adrenoceptors: do exogenous and neuronally released noradrenaline act at different sites?

    abstract：:The effects of dopamine receptor and alpha-adrenoceptor agonists and antagonists on the stimulation-evoked overflow of radioactivity from strips of dog saphenous vein previously loaded with [3H]-noradrenaline have been examined alone and in combination. In the presence of neuronal and extraneuronal catecholamine uptak...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1984.tb10098.x

    authors： Baker DJ,Drew GM,Hilditch A

    更新日期：1984-03-01 00:00:00

  • Inhibition of nitrergic neurotransmission in the bovine retractor penis muscle by an oxidant stress: effects of superoxide dismutase mimetics.

    abstract：:1. A number of superoxide dismutase (SOD) mimetics were examined both biochemically for their ability to inhibit the superoxide-catalyzed reduction of cytochrome c and nitro blue tetrazolium, and functionally for their ability to mimic authentic Cu/Zn SOD in restoring nitrergic neurotransmission in bovine retractor pe...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0701809

    authors： Mok JS,Paisley K,Martin W

    更新日期：1998-05-01 00:00:00

  • Apparent block of K+ currents in mouse motor nerve terminals by tetrodotoxin, mu-conotoxin and reduced external sodium.

    abstract：:1. In mouse triangularis sterni nerve-muscle preparations, reduced extracellular Na+ concentrations and low concentrations of the Na+ channel blocking toxins tetrodotoxin (TTX, 18-36 nM) and mu-conotoxin GIIIB (0.4-2.0 microM) selectively decreased the amplitude of the component of perineural waveforms associated with...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1992.tb14298.x

    authors： Braga MF,Anderson AJ,Harvey AL,Rowan EG

    更新日期：1992-05-01 00:00:00

  • Mechanisms of vasorelaxation induced by eicosapentaenoic acid (20:5n-3) in WKY rat aorta.

    abstract：:The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n-3), the omega-3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1 - 100 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 micro...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0703754

    authors： Engler MB,Engler MM,Browne A,Sun YP,Sievers R

    更新日期：2000-12-01 00:00:00

  • GABA and glutamate release affected by GABAB receptor antagonists with similar potency: no evidence for pharmacologically different presynaptic receptors.

    abstract：:1. The effects of a series of nine GABAB receptor antagonists of widely varying potencies on electrically stimulated release from cortical slices of [3H]-GABA in the absence or presence of 10 microM of the GABAB agonist, (-)-baclofen and of endogenous glutamate in the presence of (-)-baclofen were compared. 2. The con...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1994.tb17168.x

    authors： Waldmeier PC,Wicki P,Feldtrauer JJ,Mickel SJ,Bittiger H,Baumann PA

    更新日期：1994-12-01 00:00:00

  • Effect of iontophoretic application of cholinergic agonists and their antagonists to guinea-pig pelvic ganglia.

    abstract：:1. The electrical activity of guinea-pig pelvic ganglion cells following iontophoretically applied cholinergic drugs, alone and during orthodromic nerve stimulation via the hypogastric nerve, has been recorded intracellularly.2. Iontophoretic application of nicotine (Nic) and acetylcholine (ACh) reduced membrane resis...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1971.tb09932.x

    authors： Holman ME,Muir TC,Szurszewski JH,Yonemura K

    更新日期：1971-01-01 00:00:00

  • The effects of drugs on the sensitivity of the rat anococcygeus muscle to agonists.

    abstract：:1. The effects of cocaine, 6-hydroxydopamine (6-OHDA), reserpine and 17-beta-oestradiol on the sensitivity of the rat anococcygeus muscle to noradrenaline (NA), acetylcholine (ACh) and KCl were investigated.2. Cocaine (10(-5)M) increased the sensitivity of the anococcygeus to NA (100-fold) but not to ACh or KCl.3. 6-O...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1973.tb17261.x

    authors： Gibson A,Pollock D

    更新日期：1973-11-01 00:00:00

  • The release of a coronary vasodilator metabolite from the guinea-pig isolated perfused heart stimulated by catecholamines, histamine and electrical pacing and by exposure to anoxia.

    abstract：:1 A procedure involving two guinea-pig isolated hearts perfused in series is described for detecting in the recipient heart the release of a possible coronary vasodilator metabolite from the donor heart. 2 Adrenaline and isoprenaline stimulated the rate and force of contraction and produced a multiphasic coronary vasc...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1976.tb07696.x

    authors： Broadley KJ

    更新日期：1976-09-01 00:00:00

  • Cannabinoid CB2 receptors in human brain inflammation.

    abstract：:The presence of functional cannabinoid CB2 receptors in the CNS has provoked considerable controversy over the past few years. Formerly considered as an exclusively peripheral receptor, it is now accepted that it is also present in limited amounts and distinct locations in the brain of several animal species, includin...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1038/sj.bjp.0707505

    authors： Benito C,Tolón RM,Pazos MR,Núñez E,Castillo AI,Romero J

    更新日期：2008-01-01 00:00:00

  • Protocatechuic acid inhibits cancer cell metastasis involving the down-regulation of Ras/Akt/NF-κB pathway and MMP-2 production by targeting RhoB activation.

    abstract：BACKGROUND AND PURPOSE:Protocatechuic acid (PCA) is plentiful in edible fruits and vegetables and is thus one anti-oxidative component of normal human diets. However, the molecular mechanisms involved in the chemopreventive activity of PCA are poorly understood. Here, we investigated the mechanism(s) underlying the ant...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.2010.01022.x

    authors： Lin HH,Chen JH,Chou FP,Wang CJ

    更新日期：2011-01-01 00:00:00

  • Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin.

    abstract：:1. Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea-pig. ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1994.tb13100.x

    authors： Kanthakumar K,Cundell DR,Johnson M,Wills PJ,Taylor GW,Cole PJ,Wilson R

    更新日期：1994-06-01 00:00:00

  • [Nphe(1)]-Nociceptin (1-13)-NH(2), a nociceptin receptor antagonist, reverses nociceptin-induced spatial memory impairments in the Morris water maze task in rats.

    abstract：:1. The present study was undertaken to investigate the effects of the novel nociceptin receptor antagonist, [Nphe(1)]-Nociceptin (1-13)-NH(2) (bilateral intrahippocampal injection, 50 nmole rat(-1)) on purported nociceptin-induced (bilateral intrahippocampal injection, 5 nmole rat(-1)) deficits in spatial learning in ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0703724

    authors： Redrobe JP,Calo G,Guerrini R,Regoli D,Quirion R

    更新日期：2000-12-01 00:00:00

  • The design, synthesis and pharmacological characterization of novel β₂-adrenoceptor antagonists.

    abstract：BACKGROUND AND PURPOSE:Selective and potent antagonists for the β(2) -adrenoceptor are potentially interesting as experimental and clinical tools, and we sought to identify novel ligands with this pharmacology. EXPERIMENTAL APPROACH:A range of pharmacological assays was used to assess potency, affinity, selectivity (β...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.2011.01269.x

    authors： Hothersall JD,Black J,Caddick S,Vinter JG,Tinker A,Baker JR

    更新日期：2011-09-01 00:00:00

  • Nerve-mediated inhibition of mechanical activity in rabbit duodenum and the effects of desensitization to adenosine and several of its derivatives.

    abstract：:1. Inhibition of mechanical activity in longitudinal muscle strips of rabbit duodenum was induced by perivascular and intramural nerve stimulation.2. The effects of perivascular stimulation were abolished by phentolamine + propranolol, guanethidine, reserpine and by tetrodotoxin. The effects of intramural stimulation ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1973.tb06916.x

    authors： Weston AH

    更新日期：1973-06-01 00:00:00

  • Role of nitric oxide and septide-insensitive NK(1) receptors in bronchoconstriction induced by aerosolised neurokinin A in guinea-pigs.

    abstract：:The tachykinin, neurokinin A (NKA), contracts guinea-pig airways both in vitro and in vivo, preferentially activating smooth muscle NK(2) receptors, although smooth muscle NK(1) receptors may also contribute. In vitro evidence suggests that NKA activates epithelial NK(1) receptors, inducing the release of nitric oxide...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0703135

    authors： Ricciardolo FL,Trevisani M,Geppetti P,Nadel JA,Amadesi S,Bertrand C

    更新日期：2000-03-01 00:00:00

  • Some factors influencing the release of 5-hydroxyindol-3-ylacetic acid in the forebrain.

    abstract：:1. Electrical stimulation of the mid-brain raphé in anaesthetized adrenalectomized rats produced a significant decrease in the forebrain content of 5-hydroxytryptamine (5-HT) and an increase in the concentration of 5-hydroxyindol-3-ylacetic acid (5-HIAA).2. Stimulation of peripheral sensory nerves did not influence ei...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1970.tb09550.x

    authors： Padjen A,Randić M

    更新日期：1970-05-01 00:00:00

  • Identification of N-arachidonoyl dopamine as a highly biased ligand at cannabinoid CB1 receptors.

    abstract：BACKGROUND AND PURPOSE:N-arachidonyl dopamine (NADA) has been identified as a putative endocannabinoid, but there is little information about which signalling pathways it activates. The purpose of this study was to identify the signalling pathways activated by NADA in vitro. EXPERIMENTAL APPROACH:Human or rat cannabin...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.13341

    authors： Redmond WJ,Cawston EE,Grimsey NL,Stuart J,Edington AR,Glass M,Connor M

    更新日期：2016-01-01 00:00:00

  • Positive allosteric modulation by ivermectin of human but not murine P2X7 receptors.

    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

    authors： Nörenberg W,Sobottka H,Hempel C,Plötz T,Fischer W,Schmalzing G,Schaefer M

    更新日期：2012-09-01 00:00:00

  • Decreased synthesis of DNA in regenerating rat liver after the administration of reserpine.

    abstract：:1. Reserpine given to rats before the enhanced synthesis of DNA begins 14h after partial hepatectomy markedly depresses thymidine uptake into DNA at 24 hours.2. At this time decreased activity of liver thymidine kinase but unchanged thymidine 5'-nucleotidase were observed.3. Reserpine has no effect on DNA synthesis wh...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1973.tb08370.x

    authors： Cihák A,Vaptzarova K

    更新日期：1973-10-01 00:00:00

  • Evidence of a role for NK1 and CGRP receptors in mediating neurogenic vasodilatation in the mouse ear.

    abstract：:The aims of this study were to develop a technique to measure blood flow in the mouse ear and to investigate the nature of the vasodilator mediator(s) involved in the response to capsaicin. The response to capsaicin, applied topically, was investigated in anaesthetized CD1 or Sv129+C57BL/6 wild-type (+/+) or NK(1) rec...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0704485

    authors： Grant AD,Gerard NP,Brain SD

    更新日期：2002-01-01 00:00:00

  • Lipoic acid significantly restores, in rats, the age-related decline in vasomotion.

    abstract：BACKGROUND AND PURPOSE:The age-related decline in vasorelaxation is largely due to ceramide-induced induction of phosphatase 2A (PP2A), which limits nitric oxide synthase (eNOS) phosphorylation at stimulatory sites. We hypothesized that ceramide accumulation was from an age-related loss of endothelial glutathione (GSH)...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/bjp.2008.28

    authors： Smith AR,Visioli F,Frei B,Hagen TM

    更新日期：2008-04-01 00:00:00