Abstract：
:In the present work we evaluated the anticonvulsant effects of two novel antagonists of the glycine co-agonist site (glycineB receptor) within the N-methyl-D-aspartate (NMDA) receptor complex, MRZ 2/576 (a tricyclic pyrido-phtalazin dione derivative) and L-701,324 (7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)quinoline). As a model of epilepsy we used amygdala-kindled rats, which are considered as a model to study the efficacy of drugs against human complex partial seizures. MRZ 2/576 (2.5-10 mg/kg i.p. 15 min before testing) did not influence afterdischarge threshold, which is believed to be the most subtle indicator of efficacy against kindled seizures, nor did it affect other measures of seizure activity such as seizure severity, seizure duration and afterdischarge duration. However, MRZ 2/576 produced dose-dependent ataxia as measured in the open field and rotarod test. The highest dose tested (10 mg/kg) also markedly reduced rectal temperature (by about 1.5 degrees C). L-701,324 (2.5-10 mg/kg i.p. 30 min before testing) dose dependently and significantly increased afterdischarge threshold, but other seizure parameters remained unchanged. The ataxia produced by lower doses of L-701,324 (2.5 and 5 mg/kg) was more pronounced than that caused by MRZ 2/576. However, the ataxia observed following the higher dose of L-701,324 (10 mg/kg) was less intense than that elicited by MRZ 2/576. The behavioral alterations produced by the two drugs did not resemble those characteristic for classical competitive and uncompetitive NMDA receptor antagonists. In conclusion, our data indicate that glycineB receptor antagonists are not promising candidates for the treatment of complex partial seizures in humans, at least as monotherapy.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Wlaź P,Löscher Wdoi
10.1016/s0014-2999(97)01452-0subject
Has Abstractpub_date
1998-01-19 00:00:00pages
39-46issue
1eissn
0014-2999issn
1879-0712pii
S0014-2999(97)01452-0journal_volume
342pub_type
杂志文章abstract：:The pharmacological properties of rat and human 5-HT3 receptors expressed in Xenopus oocytes were assessed using a two-electrode voltage clamp technique. Meta-chlorophenylbiguanide (mCPBG), a 5-HT3 receptor-selective agonist, elicited typical current responses in both rat and human 5-HT3 receptor-expressing oocytes. H...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00058-8
更新日期：1999-03-12 00:00:00
abstract：:Polygonum tinctorium Lour. (P. tinctorium) is known to have the ability to suppress inflammation. We attempted to isolate the active compounds from P. tinctorium based on their inhibitory effects on the production of interferon-gamma, which is a well-known inflammatory cytokine. We thus isolated indirubin, an isomer o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00879-7
更新日期：2000-12-20 00:00:00
abstract：:In our continuing search to discover bioactive compounds from natural products, we isolated six new clerodane diterpenes, caseamembrins A to F, from Casearia membranacea and examined their antiproliferative activities in human hormone-resistant prostate cancer PC-3 cells. All of these compounds displayed effective ant...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.09.040
更新日期：2004-10-25 00:00:00
abstract：:The present study describes the effects of halothane on morphine activity in the isolated left atria of the rat. Concentration-response curves were obtained for the negative inotropic effects of morphine on electrically stimulated left atria. Morphine significantly decreased the contractile force, with an inhibitory c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90566-o
更新日期：1990-01-17 00:00:00
abstract：:The effects of brief actinomycin D treatment (0.1 microgram/ml, 0.5 h) on inhibition of cell growth and colony formation were studied in synchronized HeLa cells. Cells in late S and G2 phases were found to be maximally sensitive to inhibition of cell growth and colony formation after short exposure to actinomycin D. C...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(94)90064-7
更新日期：1994-04-04 00:00:00
abstract：:Inhibition of the thromboxane A2-synthesizing enzyme (DP-1904: [+/-]-6-[1-imidazolylmethyl]-5,6,7,8-tetrahydronaphthalene-2-carbo xylic acid hydrochloride hemihydrate) reportedly suppresses intercellular adhesion molecule-1 (ICAM-1) expression on the surface of stimulated vascular endothelial cells (Ishizuka et al., 1...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00478-5
更新日期：1996-10-03 00:00:00
abstract：:We investigated the effects of an L-type and N-type Ca(2+) channel blocker, cilnidipine, on neurally mediated chronotropic responses to clarify the anti-autonomic profile of cilnidipine in anesthetized dogs. Pretreatment with cilnidipine (0.3, 1.0 and 3.0 microg/kg, i.v.), which decreased mean blood pressure by 5 to 3...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00738-5
更新日期：2001-02-09 00:00:00
abstract：:Electrical stimulation produced a contraction in the isolated guinea-pig vas deferens. This response was blocked by tetrodotoxin, guanethidine and bretylium but not by atropine. The magnitude of the contractile response to electrical stimulation depended on the concentration of the external calcium. Sulfur-containing ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90262-5
更新日期：1983-11-11 00:00:00
abstract：:Mitomycin C (MMC) is known to reduce epidural fibrosis, but the underlying mechanisms have not yet been elucidated. Aberrant miR-200b expressions have been reported in multiple types of fibrotic tissues from many diseases. The aim of this study was to clarify the mechanism by which MMC induces fibroblasts apoptosis an...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.08.002
更新日期：2015-10-15 00:00:00
abstract：:The aim of the present study was to determine whether U50,488H (a selective kappa-opioid receptor agonist) inhibits cardiac hypertrophy and fibrosis induced by beta-adrenoceptor stimulation in a rat model. Cardiac hypertrophy and fibrosis were developed by intraperitoneal administration of isoprenaline (ip. 3.0 mg/kg/...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.01.050
更新日期：2009-04-01 00:00:00
abstract：:The effects of delta9-THC and its ethanol vehicle on pilocarpine-induced parotid gland secretions were investigated in rats. Single doses of delta9-THC (1, 2.5, 5 and 10 mg/kg) or 95% ethanol were administered i.v. prior to pilocarpine stimulation of saliva. Total flow, alpha-amylase and cation content of the induced ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90071-6
更新日期：1976-12-01 00:00:00
abstract：:AQA39 is a new cardioactive agent with, at low dosages, a minute positive inotropic action on ventricular myocardial tissue probably mediated through the calcium sequestering membraneous systems. At higher concentrations AQA39 depressed myocardial performance probably due to inhibition of the slow calcium channels. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90186-9
更新日期：1984-08-03 00:00:00
abstract：:The effect of some tryptaminergic drugs on electroshock fighting behaviour in rats was determined. Reserpine and tetrabenazine reduced the fighting responses while 5-hydroxytryptophan increased the fighting responses in normal as well as reserpine-treated animals. p-Chlorophenylalanine, a specific depletor of brain se...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90149-7
更新日期：1976-10-01 00:00:00
abstract：:Major depression is a prevalent and debilitating disorder and a substantial proportion of patients fail to reach remission following standard antidepressant pharmacological treatment. Limited efficacy with currently available antidepressant drugs highlights the need to develop more effective medications for treatment-...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2014.10.063
更新日期：2015-04-15 00:00:00
abstract：:After incubation of rat cortical cell cultures with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 12 h, cells showed fragmentation of DNA at internucleosomal linkers, the characteristic feature of apoptosis. In a quantitative approach, it was determined that the percentage of DNA fragmentation...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(92)90063-2
更新日期：1992-07-01 00:00:00
abstract：:Forskolin, a potent activator of adenylate cyclase, and isoprenaline, an unselective beta-adrenoceptor agonist, were studied in vitro on tissues from guinea-pig with respect to relaxation of the carbachol-contracted trachea, increase in the force of contraction of the papillary muscle and depression of subtetanic cont...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90780-0
更新日期：1985-06-19 00:00:00
abstract：:Administration of methyl-beta-carboline-3-carboxamide (FG 7142, 15 mg/kg i.p.) to rats has previously been shown to cause a selective increase in the levels of 3,4-dihydroxy-phenylacetic acid (DOPAC) in the prefrontal cortex and ventral tegmental area (VTA) via an interaction with benzodiazepine receptors. On withdraw...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90221-4
更新日期：1987-06-04 00:00:00
abstract：:The anti-arrhythmic action of 2,3-cis-1,2,3,4-tetrahydro-5-[(2-hydroxy-3-tert-butylamino)propoxy]2,3-naphthalenediol (nadolol) was evaluated and compared with that of propranolol in several experimental models of cardiac arrhythmias. Both nadolol and propranolol antagonized isoproterenol-induced tachycardia and ouabai...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90296-x
更新日期：1976-01-01 00:00:00
abstract：:Thoracic preganglionic sympathetic nerve activity, blood pressure, heart rate and femoral arterial conductance were recorded in anaesthetised, paralysed cats. Cumulative dose-response curves were constructed for 8-OH-DPAT, ipsapirone and clonidine. All three drugs caused dose-related falls in blood pressure which were...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90431-6
更新日期：1987-06-19 00:00:00
abstract：:Cocaine is eliminated and detoxified principally through the metabolism of nonspecific plasma and tissue esterases. Microsomal oxidative metabolism is of importance in cocaine N-demethylation, this being a principal pathway of cocaine bioactivation and hepatotoxicity. The contribution of different cytochrome P450 (CYP...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(94)90078-7
更新日期：1994-01-03 00:00:00
abstract：:Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. Th...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2015.03.047
更新日期：2015-07-15 00:00:00
abstract：:Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine. By means of alkaline phosphatase activity and osteocalcin enzyme-linked immunosorbent assay (ELISA), we have shown that piceatannol exhibits a significant induction of differentiation in immortalized fetal osteoblasts (hFOB...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.08.073
更新日期：2006-12-03 00:00:00
abstract：:Plasma concentrations of unchanged dihydroergotamine (DHE) were measured in beagle dogs on days 1 and 7 of a 1 week treatment with daily oral doses of DHE. Responses to both 5-HT and noradrenaline were monitored isometrically on spiral strips from saphenous arteries and femoral veins removed 24 and 72 h after the last...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90601-5
更新日期：1983-04-22 00:00:00
abstract：:The recent elucidation of the primary structures of different melatonin receptors as well as the deduction of the secondary structure of rhodopsin has allowed us to construct a model for melatonin recognition at its G protein-coupled receptor. To achieve this, we have used the quantum mechanics method Austin model 1 t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00114-8
更新日期：1996-05-23 00:00:00
abstract：:A characteristic of endothelia damage and repair is the turnover of extracellular matrix components. As a part of extracellular matrix glycosaminoglycan (GAG), hyaluronic acid (HA, main component of glycocalyx) is not only involved in inflammation, proliferation, differentiation of cells, and tissue remodeling, but al...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.172413
更新日期：2019-08-05 00:00:00
abstract：:Endogenous opioid and nociceptin systems are widely distributed in the gastrointestinal tract where they seem to play a crucial role in maintaining the intestinal homeostasis. The aim of our study was to assess whether activation of nociceptin (NOP) and µ-opioid (MOP) receptors by a mixed NOP/MOP receptor agonist, BU0...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.09.021
更新日期：2015-10-15 00:00:00
abstract：:We investigated the effects of the platelet activating factor (PAF) receptor antagonists, SM-12502 ((+)-cis-3,5-dimethyl-2-(pyridyl)- thiazolidin-4-one hydrochloride), WEB-2086 (3-(4-(2-chlorphenyl)-9-methyl-6H-thieno(3,2-f)-(1,2,4)triazolo(4, 3- a)(1,4)diazepin-2-yl)-1-(4-morpholinyl)-1-propanone) and RP-48740 (3-(3-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(94)90037-x
更新日期：1994-11-15 00:00:00
abstract：:Pretreatment of chick biventer cervicis preparations with ethanol (290 mM) potentiated the EC50 of choline, acetylcholine, carbachol and phenyltrimethylammonium 91%, 319%, 97% and 213%, respectively. Perhaps this interaction of ethanol and neurotransmitter could contribute to the effects on coordination and motor acti...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90165-x
更新日期：1980-01-25 00:00:00
abstract：:Graft-versus host disease (GVHD) remains the most significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dissociation of graft versus-leukemia (GVL) activity from GVHD has yet to be achieved. In this study, we used γ-secretase inhibitor (GSIs, DAPT) to inhibit Notch signaling in GV...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.10.004
更新日期：2019-01-15 00:00:00
abstract：:(5R)-5-hydroxytriptolide (LLDT-8) exhibits strong immunosuppressive activities in vitro and in vivo. Here, we investigated the effects of LLDT-8 on concanavalin A-induced hepatitis. Liver damage was evaluated by serum alanine transaminase (ALT) level and liver histology. The effects of LLDT-8 were determined by measur...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.03.013
更新日期：2006-05-10 00:00:00
