Abstract:
:The aim of this study was to determine the effects of 4-(4-bromophenyl)-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (TP4-a new S-triazole derivative possessing anticonvulsant properties in preclinical studies) on the protective action of four different classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) against maximal electroshock-induced seizures in mice. Results indicate that TP4 administered intraperitoneally at doses of 75 and 100 mg/kg significantly elevated the threshold for electroconvulsions in mice. TP4 at doses of 12.5, 25, 37.5 and 50 mg/kg had no impact on the threshold for electroconvulsions in mice. Moreover, TP4 (50 mg/kg) significantly enhanced the anticonvulsant activity of carbamazepine, phenobarbital and valproate, but not that of phenytoin in the maximal electroshock seizure test in mice. TP4 at 25 mg/kg significantly potentiated the anticonvulsant action of carbamazepine, but not that of phenobarbital, phenytoin and valproate in the mouse maximal electroshock-induced seizure model. Pharmacokinetic experiments revealed that TP4 significantly elevated total brain concentrations of carbamazepine and valproate, having no impact on total brain concentrations of phenobarbital in mice. In conclusion, the enhanced anticonvulsant action of phenobarbital by TP4 was probably pharmacodynamic in nature and, therefore, the combination of TP4 with phenobarbital is worthy of consideration while extrapolating the results from this study into clinical settings. The enhanced anticonvulsant action of carbamazepine and valproate by TP4 in the mouse maximal electroshock-induced seizure model was associated with pharmacokinetic increases in total brain concentrations of the antiepileptic drugs in mice. The combination of TP4 with phenytoin was neutral from a preclinical point of view.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Luszczki JJ,Plech T,Wujec Mdoi
10.1016/j.ejphar.2012.06.023subject
Has Abstractpub_date
2012-09-05 00:00:00pages
99-106issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(12)00535-3journal_volume
690pub_type
杂志文章abstract::Binding sites for the sigma ligand [3H]di-o-tollylguanidine ([3H]DTG) have been reported to be altered in the brains of genetically dystonic rats. In the present study, selective sigma 1 and sigma 2 assay conditions were utilized in an effort to define which subpopulation of [3H]DTG binding sites is altered in the dys...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90399-3
更新日期:1993-12-07 00:00:00
abstract::The purpose of this study is to clarify involvement ratios between central and peripheral cyclooxygenase (COX)-2 in rat inflammatory pain models, by evaluating celecoxib and [6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid (CIAA) on carrageenan-induced mechanical and thermal hyperalgesia. Celecoxib and CIAA exh...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.07.063
更新日期:2008-01-06 00:00:00
abstract::A few decades ago, cardiac muscle was discovered to possess signalling pathways that, when activated, protect the myocardium against the damage induced by ischaemia-reperfusion. The ability of cardiac muscle to protect itself against injury has been termed 'cardioprotection'. Many compounds and procedures can trigger ...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2018.06.029
更新日期:2018-08-15 00:00:00
abstract::Isolated porcine myocardial trabeculae from right atria and left ventricles were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Alpha calcitonin gene-related peptide (alpha-CGRP) increased contractile force in nearly half of the trabeculae, whereas th...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00721-9
更新日期:1999-12-03 00:00:00
abstract::Quantitative characterization of the kappa opioid receptor in the rabbit ear artery was carried out using three kappa-selective agonist compounds, dynorphin-(1-13), U-69593 and ethylketocyclazocine. Kinetic analysis was performed using the antagonist, MR 2266. Two other in vitro preparations were studied for compariso...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90542-0
更新日期:1988-07-14 00:00:00
abstract::Using 3H-ligands and radioactive microspheres we studied the binding characteristics and the effects on the distribution of carotid arterial blood flow of n-(3-acetylaminophenyl)piperazine hydrochloride (BEA 1654). The compound had a Ki value of 32 nM (5-HT: 8 nM) on 5-HT1 but no or very weak affinity for 5-HT2, alpha...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90259-6
更新日期:1985-01-08 00:00:00
abstract::The effects of two predominant dopamine D2-like receptor agonists, talipexole (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo [4,5-d]-azepine dihydrochloride, B-HT 920 CL2) and pramipexole (S(-)2-amino-4,5,6,7-tetrahydro-6-propyl-aminobenzothiazole dihydrochloride, SND 919 CL2Y), were studied alone and in combination ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)00129-5
更新日期:1997-05-01 00:00:00
abstract::We have previously proposed that pro-inflammatory cytokines and nitric oxide (NO) contributed to reversible myocardial depression in patients with sepsis and congestive heart failure. Sepsis and heart failure are also associated with refractoriness to beta-adrenoceptor agonists. Therefore, the chronotropic effects of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(96)00912-0
更新日期:1997-02-12 00:00:00
abstract::The effects of cannabinoid drugs on cAMP production were examined in mammalian brain. The cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3,-d,e-1,4-benzoxazin-6-yl]-(1-naphthalenyl) methanone (WIN55,212-2) decreased forskolin-induced cAMP accumulation in a concentration...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)01575-3
更新日期:2002-05-17 00:00:00
abstract::Inhibitors of Na(+)/H(+) exchanger (NHE) 1 have been shown to exert protective effects on various myocardial injuries. In this study, we characterized the pharmacodynamic properties of new guanidine NHE1 inhibitors (cariporide, sabiporide, KR-32511, KR-32570, and KR-33028) to analyze their myocardial protective effect...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.03.056
更新日期:2007-07-12 00:00:00
abstract::We studied the effects of 2-(allyl-1-piperazinyl)-4-n-amyloxyquinazoline fumarate (KB-5666) on brain edema and histological neuronal damage in rats with focal ischemia and on lipid peroxidation in brain homogenates and brain mitochondria in vitro. KB-5666 (3-100 microM) inhibited lipid peroxidation in brain homogenate...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90367-y
更新日期:1991-05-02 00:00:00
abstract::We have characterized the tachykinin NK(2) receptor-mediated contraction and vectorial ion transport responses in the muscularis mucosae and mucosa of the rat isolated distal colon, respectively. The tachykinin NK(2) receptor-selective antagonist nepadutant (c([(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta))) p...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)00836-6
更新日期:2001-03-01 00:00:00
abstract::The binding characteristics of compound 48/80 were examined using rat mast cells and fractionated 14C-labeled compound 48/80 components at 4 degrees C in vitro where no degranulation of the cells occurred. The binding potencies of these components in the presence of Ca2+ generally paralleled their histamine releasing ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90688-0
更新日期:1985-09-24 00:00:00
abstract::Blood pressure responses to intrathecal (i.t.) injection of neurochemicals were examined in the fructose-fed rat, an experimental model of metabolic syndrome.Sprague-Dawley rats receiving either tap water or water containing 10% fructose during 8 weeks were anesthetized with sodium pentobarbital. The endocannabinoid a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.02.037
更新日期:2013-04-15 00:00:00
abstract::This study evaluated the coronary dopamine receptors by using the dopamine D1 receptor agonist fenoldopam, dopamine D2 receptor agonist propylbutyldopamine, and their selective antagonists SCH23390 and domperidone. Left circumflex coronary flow (CF), coronary perfusion pressure at constant flow, left ventricular hemod...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)94126-i
更新日期:1990-11-06 00:00:00
abstract::Cell-cell interaction through binding of intercellular adhesion molecule (ICAM), B7.1, B7.2 and CD40 on monocytes to their ligands on T-cells plays a number of roles in cytokine . High mobility group box 1 (HMGB1), an abundant and conserved nuclproduction and lymphocyte proliferationear protein, acts in the extracellu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.11.058
更新日期:2013-02-15 00:00:00
abstract::Inflammation is a primary event in atherogenesis. Oleoylethanolamide (OEA), a naturally occurring fatty-acid ethanolamide, lowers lipid levels in liver and blood through activation of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPARα). We designed and synthesized (Z)-(S)-9-octadecenamide, N...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.04.009
更新日期:2011-06-25 00:00:00
abstract::In the presence of RS-15385-197 to preclude binding to alpha 2-adrenoceptors, [3H]p-aminoclonidine labelled a low affinity high capacity site, (Kd = 127.6 +/- 19.7 nM, Bmax 978 +/- 172 fmol/mg protein) whereas [3H]idazoxan labelled a high affinity low capacity site (Kd = 1.66 +/- 0.28 nM, Bmax 45.3 +/- 11.4 fmol/mg pr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90731-v
更新日期:1993-02-23 00:00:00
abstract::Brain microvessel endothelial cell monolayers have been shown to be a suitable blood-brain barrier in vitro system to study adrenergic regulation of permeability. We tested adrenergic drugs on bovine brain microvessel endothelial cell monolayer permeability to a biomembrane impermeant molecule, sodium fluorescein. End...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(94)90092-2
更新日期:1994-10-14 00:00:00
abstract::Transient activation of the outward K+ current caused by a rise in the cytosolic free Ca2+ concentration, [Ca2+]i was the predominant change in plasma membrane ion flux during the first phase of thyrotropin-releasing hormone (TRH) action on pituitary cells. Following the intracellular application of inhibitors of 1,2-...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(89)90046-1
更新日期:1989-03-07 00:00:00
abstract::In primary cultured striatal neurons we found that (+-)-trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) could inhibit forskolin-induced cAMP formation in a dose-dependent manner (EC50 156 +/- 38 microM, n = 5, maximal inhibition 37.8 +/- 1.2, n = 37). The trans-ACPD-induced inhibition was totally abolished in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(92)90112-9
更新日期:1992-04-10 00:00:00
abstract::We isolated a novel peptide, calcitonin receptor-stimulating peptide-1 (CRSP-1), from porcine brain and found that the administration of this peptide into rats induced a transient decrease in plasma calcium concentration. Therefore, we investigated the effects of CRSP-1 on osteoclastogenesis. Osteoclast-like cells wer...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.01.034
更新日期:2007-04-10 00:00:00
abstract::Thiazolidinedione and isoxazolidinedione insulin sensitizers activate peroxisome proliferator-activated receptor gamma (PPAR gamma). Some thiazolidinediones modify ion channels in smooth muscles; however, the mechanism by which their actions occur has not been clarified. We, thus, examined the effects of three thiazol...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01047-0
更新日期:2001-06-29 00:00:00
abstract::D-amino acid oxidase (DAAO) is an astroglial enzyme abundantly present in the pain sensing regions including brain and spinal cord. There have been studies indicating an upregulation and increased activity of DAAO in different pain models. Furthermore, the upregulation of DAAO also results in the development of morphi...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2019.05.001
更新日期:2019-07-15 00:00:00
abstract::The hypothesis that K(+) channels and cell depolarization are involved in neuronal death and neuroprotection was tested in bovine chromaffin cells subjected to two treatment periods: the first period (preconditioning period) lasted 6 to 48 h and consisted of treatment with high K(+) solutions or with tetraethylammoniu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.08.084
更新日期:2006-12-28 00:00:00
abstract::The GABA-inhibitory action of bicuculline on lobster muscle was critically re-examined. Bicuculline (20-100 micrometers) depressed the GABA-evoked conductance increase in a reversible manner, the double reciprocal transformation of the GABA dose/conductance curves remaining linear. If bicuculline was assumed to be a p...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90428-3
更新日期:1981-03-05 00:00:00
abstract::The selectivity of the potent dopamine D-2 agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) was examined in a series of in vivo and in vitro pharmacological models. In radioligand binding assays, N-0437 showed high potency (Ki = 0.69 nM) and selectivity for D-2 receptors as compared to its potency...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90783-2
更新日期:1988-03-01 00:00:00
abstract::Ro 40-5967 [(1S,2S)-2-[2[3-(2-benzamidopropyl]- methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl- methoxyacetate] is a new Ca2+ channel antagonist active at L-type channels. Radioligand binding studies in cardiac tissue show that Ro 40-5967 does not inhibit 1,4-dihydropyridine binding, but does in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00194-p
更新日期:1995-07-04 00:00:00
abstract::The effect of A-317491 (5-([(3-Phenoxybenzyl)[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl)-1,2,4-benzenetricarboxylic acid), a recently described selective P2X3 and P2X(2/3) receptor antagonist, on inflammatory mechanical hyperalgesia was examined. In the rat Freund's complete adjuvant model of inflammatory ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.09.056
更新日期:2004-11-03 00:00:00
abstract::We investigated the effects of three bile acids conjugated with N-acetylglucosamine, ursodeoxycholate N-acetylglucosaminide, tauroursodeoxycholate N-acetylglucosaminide and glycoursodeoxycholate N-acetylglucosaminide, on bile flow and biliary excretion of various markers in comparison with ursodeoxycholic acid, taurou...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00725-0
更新日期:1998-12-11 00:00:00