Abstract：
:We assessed the effects of active site-directed, fibrinogen recognition exosite (FRE)-directed and bifunctional thrombin inhibitors, on shear-induced platelet reactivity (adhesion/aggregation) and dynamic coagulation (coagulation of flowing blood). An in vitro test for shear-induced haemostatic plug formation and dynamic coagulation (haemostatometry) was employed using non-anticoagulated rat blood. The active site-directed inhibitors (argatroban, P891, P899) caused inhibition of platelet reactivity and coagulation at 1-, 100- and 100-microM concentrations, respectively. Bifunctional inhibitors (P553, P1053) exerted inhibitory effects at 0.1 microM. A dimeric bifunctional inhibitor P824 caused significant inhibition at 1 microM. The FRE-directed inhibitor (P960) inhibited shear-induced platelet reactivity at 10 microM but the dynamic coagulation at 1 microM. Combination of active site-directed argatroban and FRE-directed P960 did not show any synergistic effect. The most potent inhibition was observed in monomeric bifunctional inhibitors. The inhibitory effects were compared with the K(i) values against human thrombin and with the IC(50) values against fibrin clot formation. The minimum effective concentrations on shear-induced platelet reactivity and dynamic coagulation were comparable with the IC(50) values, but not with the K(i) values.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Taka T,Konishi Y,Slon-Usakiewicz J,Medvedkin V,Tsuda Y,Okada Y,Seki J,Yamamoto Jdoi
10.1016/s0014-2999(00)00655-5keywords:
subject
Has Abstractpub_date
2000-10-13 00:00:00pages
181-9issue
2eissn
0014-2999issn
1879-0712pii
S0014-2999(00)00655-5journal_volume
406pub_type
杂志文章abstract：:We examined the mechanism of the inflammatory response induced by topical application of mustard oil (0.5-20.0%/20 microliters per ear) to the mouse ear compared to that of the response to capsaicin. The dose-dependent increases in plasma extravasation and ear thickness reached a maximum at approximately 30 min after ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01040-6
更新日期：1997-08-27 00:00:00
abstract：:To test the hypothesis that serotonergic modulation of the effects of phencyclidine (PCP) are due to circuit- rather than receptor-based interactions between glutamatergic and serotonergic systems, multivariate profiles of rat behavior were assessed after treatments with the 5-hydroxytryptamine (5-HT) 5-HT2 receptor a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01557-4
更新日期：1998-02-19 00:00:00
abstract：:beta-Funaltrexamine (beta-FNA) bound to mouse brain membranes in a reversible and an irreversible (not removed by washing of the membrane) manner, and a portion of each type of binding was opioid-specific. Addition of 100 mM NaCl to the incubating medium enhanced the binding of beta-FNA to membranes. Using membranes p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90257-2
更新日期：1985-01-08 00:00:00
abstract：:A possible cross-competition between vasoactive intestinal peptide (VIP) and somatostatin (somatotropin release inhibiting factor; SRIF) and their respective receptors, was investigated at native or recombinant SRIF and VIP/pituitary adenylate cyclase-activating polypeptide (PACAP) receptors. The activity of VIP was e...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01223-7
更新日期：2001-08-31 00:00:00
abstract：:Two major effector systems are frequently implicated in the immune and endothelial cell alternations associated with inflammation. They include the enhanced production of reactive oxygen species and diminished bioavailability of nitric oxide (NO). Importantly, these processes can be regulated by endogenously produced ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.05.001
更新日期：2013-08-05 00:00:00
abstract：:The highly toxic monomer 12-deoxyphorbol 13-palmitate (G) was extracted from the roots of Euphorbia fischeriana. Our experimental data confirmed studies showing that 12-deoxyphorbol 13-palmitate had certain antitumor activities. The MTT method, soft agar experiments, and nude mouse tumor experiments proved that 12-deo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.11.015
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abstract：:The present study has examined the effects and the possible mechanisms of a single dose of simvastatin on the severity of arrhythmias resulting from a 25min occlusion and reperfusion of the left anterior descending coronary artery in anaesthetized (chloralose and urethane) dogs. The control animals (n=16) were given t...
journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2014.03.021
更新日期：2014-06-05 00:00:00
abstract：:The behavioral effects of methamphetamine (METH) are mediated by the striatum, which is divided into the patch compartment, which mediates limbic and reward functions, and the matrix compartment, which mediates sensorimotor tasks. METH treatment results in repetitive behavior that is related to enhanced relative activ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.01.001
更新日期：2017-02-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01555-0
更新日期：1998-02-26 00:00:00
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journal_title：European journal of pharmacology
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更新日期：2017-11-15 00:00:00
abstract：:Translational research for neurodegenerative disease depends intimately upon animal models. Unfortunately, promising therapies developed using mouse models mostly fail in clinical trials, highlighting uncertainty about how well mouse models mimic human neurodegenerative disease at the molecular level. We compared the ...
journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2015.03.021
更新日期：2015-07-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.05.024
更新日期：2004-07-08 00:00:00
abstract：:The role of flexibility of the alkyl side chain in the tetrahydrocannabinols to cannabinoid activity has been delineated in previous studies with side chain analogs of Delta(8)-tetrahydrocannabinol with double or triple bonds. This study investigated the site of antinociceptive action for these analogs through analysi...
journal_title：European journal of pharmacology
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doi：10.1016/s0014-2999(00)00259-4
更新日期：2000-06-02 00:00:00
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journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2011.10.003
更新日期：2011-12-15 00:00:00
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journal_title：European journal of pharmacology
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doi：10.1016/s0014-2999(00)00392-7
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90448-0
更新日期：1985-02-05 00:00:00
abstract：:Meperidine has atypical opioid receptor agonist effects and shares some structural features with the phenyltropane (WIN) analogs of cocaine. In combination with 0.1 mg/kg naltrexone, meperidine produced cocaine-like discriminative stimulus effects in monkeys, whereas morphine was inactive. Both cocaine and meperidine ...
journal_title：European journal of pharmacology
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doi：10.1016/0014-2999(95)00696-6
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abstract：:Clopidogrel is not safe enough for the gastric mucosa in patients with high risk of peptic ulcer. This study aimed to explore if clopidogrel delays gastric ulcer healing and elucidate the involved mechanisms. Gastric ulcer was induced in rats and the ulcer size, mucosal epithelial cell proliferation of the ulcer margi...
journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2012.07.054
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.07.004
更新日期：2014-10-15 00:00:00
abstract：:Eleutheroside E (EE), a principal component of Eleutherococcus senticosus, has been reported to have anti-inflammatory and protective effects in ischemia heart etc. However, whether it can mitigate behavioral alterations induced by sleep deprivation, has not yet been elucidated. Numerous studies have demonstrated that...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.02.036
更新日期：2011-05-11 00:00:00
abstract：:The cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) has a higher affinity for the dopamine transporter and may be potentially useful in interfering with cocaine's actions in brain. However, imaging studies have demonstrated displacement of tracer doses of [123I]RTI-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00698-2
更新日期：1996-01-25 00:00:00
