Abstract:
:cRNA encoding the human IsK protein was injected into Xenopus oocytes and the expressed channels were investigated using the two-microelectrode voltage-clamp method. The novel class III antiarrhythmic NE-10064 (1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]-amino]-3- [4-(4-methyl-1-piperazinyl)-butyl]-2,4-imidazolidinedione dihydrochloride) was tested for its ability to block these channels. The compound displayed potent inhibitory effects with an EC50 of 5.4 microM. The block caused by NE-10064 was use-dependent, i.e. channels had to be activated for the inhibition to occur. Further, the reversal of the inhibition during the wash-out period was use-dependent. Finally, the blockade of human IsK channels by NE-10064 appeared to be voltage-dependent, being more pronounced at depolarized potentials. We conclude that this novel class III antiarrhythmic is a potent inhibitor of human IsK channels and suggest that such effects could be involved in its antiarrhythmic action.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Busch AE,Herzer T,Takumi T,Krippeit-Drews P,Waldegger S,Lang Fdoi
10.1016/0014-2999(94)90632-7subject
Has Abstractpub_date
1994-10-13 00:00:00pages
33-7issue
1eissn
0014-2999issn
1879-0712pii
0014-2999(94)90632-7journal_volume
264pub_type
杂志文章abstract::In urethane-anesthetized rats, the effects of intravenous injections of morphine, levorphanol, dextrorphan, pentazocine and naloxone were studied studied on the activity in nerve fibres of the cervical sympathetic trunk, and on mean arterial blood pressure and heart rate. Impulse frequency in sympathetic nerve fibres ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90032-3
更新日期:1984-05-18 00:00:00
abstract::The weak aminotetralin stimulants, (+)-AJ 76, cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin and (+)-UH 232, cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, were tested for their effects on firing rates of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNPC). (+)-AJ 76 and (+)-UH 232 a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90280-j
更新日期:1990-07-03 00:00:00
abstract::This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.08.017
更新日期:2016-11-15 00:00:00
abstract::Slices of rat kidney cortex were incubated in [3H]noradrenaline, then placed in a flow cell and subjected to electrical field stimulation. At a stimulation frequency of 5 Hz, both the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the alpha 1-adrenoceptor antagonist prazosin (0.1 microM) significantly enhan...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90026-5
更新日期:1989-10-10 00:00:00
abstract::Neither the chronic administration (40 daily subcutaneous injections) of nicotine (0.4 mg/kg) nor its withdrawal (3 days) influenced avoidance of the more aversive open runways of an elevated X-maze in rats which had been habituated to the apparatus. Lesions of the serotonergic fibres innervating the hippocampus incre...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90278-0
更新日期:1987-09-11 00:00:00
abstract::Pyrethroid insecticides have been reported to increase transmembrane sodium influx and inhibit ion-dependent ATPases in insect, squid, and toad nerve tissues. Since changes in sarcolemmal ion fluxes and inhibition of membrane-bound ATPases can alter myocardial contractility, the effects of a potent synthetic pyrethroi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90279-6
更新日期:1984-03-02 00:00:00
abstract::Many studies have demonstrated that cyclophosphamide (CPA) can affect hepatic cytochrome p450 (CYP) isoenzyme activity in animals. We have investigated the effect of CPA on gene expression of various CYP enzymes as well as beta-actin in the human acute promyelocytic leukemia cell line (HL-60S) and its multidrug-resist...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)01995-7
更新日期:2002-08-09 00:00:00
abstract::Stimulation of the right trigeminal ganglion in pentobarbital anaesthetised rats increased mean arterial blood pressure and decreased right carotid vascular resistance but had no effect on left carotid vascular resistance. Sumatriptan (0.3 mg/kg i.v.) pretreatment did not significantly affect basal levels or stimulati...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00231-9
更新日期:1995-07-25 00:00:00
abstract::Dopamine agents (saline in control groups) were coadministered with indomethacin by either single or repeated application. The ulcerogenic effect (erosions and/or ulcers) of repeated given indomethacin on gastric mucosa differed clearly from that on intestinal mucosa. The effect on intestinal mucosa was markedly great...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90253-1
更新日期:1988-12-06 00:00:00
abstract::The activation of eosinophils with the lipid mediator, leukotriene B(4), induces their homotypic aggregation. Upon activation with leukotriene B(4), eosinophils release a significant amount of arachidonic acid, a process dependent on the activation of phospholipase A(2). Here, we have evaluated whether arachidonic aci...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00697-4
更新日期:1999-11-19 00:00:00
abstract::Recently published studies have suggested that behavioral and neurochemical changes induced by selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors are potentiated by coadministration of a 5-HT1A receptor antagonist. The potentiating effect is hypothesized to be due to antagonism of somatodendritic 5-HT...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01199-0
更新日期:1997-09-10 00:00:00
abstract::6"-O-succinylapigenin [apigenin-7-O-(6'-O-succinyl)-glucoside], a novel compound, is identified in chamomile. Although it is highly produced by Bacillus amyloliquefaciens FJ18, its bioactivity remains unknown. The neuroprotective effects and antioxidative mechanism of 6''-O-succcinylapigenin in the middle cerebral art...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.03.024
更新日期:2019-07-15 00:00:00
abstract::Contractile responses to endothelin, 5-hydroxytryptamine (5-HT), noradrenaline and potassium were obtained on isolated preparations of pulmonary artery from rats made pulmonary hypertensive by an injection of monocrotaline (105 mg/kg s.c.) 4 weeks previously. When compared with data obtained in control rats, the poten...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90524-a
更新日期:1990-02-06 00:00:00
abstract::Recent data show that corticolimbic expression of the effector immediate early gene Arc is up-regulated by standard antidepressant drugs. Here, we tested the effect upon Arc expression of a novel antidepressant and selective 5-hydroxytryptamine/noradrenaline reuptake inhibitor (SNRI), (-)1-(1-dimethylaminomethyl) 5-me...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.03.002
更新日期:2004-04-12 00:00:00
abstract::Intracellular recordings were made from myenteric neurons of the guinea-pig duodenum and the responses to local ejection of several substance P (SP) analogs were examined. It was found that senktide (succinyl-[Asp6,Me-Phe8]SP-(6-11)), a selective analog for the NK-3 (SP-N) receptor, was particularly effective in depol...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90612-7
更新日期:1988-08-24 00:00:00
abstract::The relation of the structure of 31 quaternary ammonium compounds (28 inhibitors; 3 substrate analogues) with their effects on the activity of acetylcholinesterase (EC 3.1.1.7; AChE) was studied. The compounds were structurally related to the natural substrate acetylcholine (ACh). All bear a trimethylammonium moiety a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(89)90007-2
更新日期:1989-05-11 00:00:00
abstract::The actions of iontophoretically applied quipazine (QPZ) and 6-chloro-2-[1-piperazinyl]-pyrazine (CPP) were compared with those of serotonin (5-HT) on rat spinal motoneurones. QPZ and CPP qualitatively resembled 5-HT in that both facilitated single unit activity evoked by glutamate. Like 5-HT, the facilitation they pr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90600-8
更新日期:1982-06-16 00:00:00
abstract::Adenosine has been reported to have beneficial effects against ischemic brain damage, although the mechanisms are not fully clarified. To examine the role of adenosine on the ischemia-evoked release of neurotransmitters, we applied a highly selective agonist for adenosine A1 receptor, 2-chloro-N6-cyclopentyladenosine ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00559-7
更新日期:1998-09-18 00:00:00
abstract::The bisquaternary compound dequalinium has been tested for its ability to inhibit the loss of K+ which angiotensin II causes in guinea-pig hepatocytes and which occurs through apamin-sensitive Ca(2+)-activated K+ (SKCa) channels. Dequalinium blocked angiotensin II-evoked K+ loss with an IC50 of 1.5 +/- 0.1 microM and ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90590-e
更新日期:1993-05-19 00:00:00
abstract::This study was designed to assess whether nitroglycerin would improve the relationship between O2 supply and O2 consumption in the reperfused ischemic dog myocardium. In 16 dogs the left anterior descending coronary artery was occluded for 2 h, followed by a 4 h period of reperfusion. In 8 of the 16 dogs, an infusion ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90069-1
更新日期:1989-07-18 00:00:00
abstract::Activation of imidazoline receptors in the central nervous system has protective effect on several types of arrhythmias. We demonstrated that centrally administered rilmenidine, a selective imidazoline receptor agonist, prevented adrenaline-induced arrhythmias during halothane anaesthesia. However, detailed myocardial...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.08.035
更新日期:2010-11-25 00:00:00
abstract::A concentration-dependent relaxant effect of phentolamine was demonstrated in guinea-pig isolated trachea and was probably unrelated to its alpha-adrenoceptor blocking action. The maximal effect of phentolamine against spontaneous tracheal tone was in the 24-100% range. However, phentolamine produced 100% relaxation w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90534-b
更新日期:1992-02-11 00:00:00
abstract::Arvanil is a metabolically stable hybrid between anandamide and capsaicin. The present study was designed to test the role of the vagal pathway in post-arvanil respiratory and blood pressure responses. Respiratory and pressure changes evoked by an intravenous injection of arvanil were investigated in 21 urethane-chlor...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.06.012
更新日期:2010-09-15 00:00:00
abstract::The goals of the work reported here were (i) to identify distinct GABA(A)/benzodiazepine receptors in the rat hippocampus and olfactory bulb using receptor binding assays, and (ii) to determine the affinities and selectivities of benzodiazepine receptor ligands from structurally diverse chemical families at each site ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00398-8
更新日期:2000-07-21 00:00:00
abstract::Rhein is one of the anthraquinones components of Rheum. It shows excellent clinical efficacy and is widely used in the management of several disease conditions including tumors, inflammation, diabetic nephropathy, and viral infections. In this review, we summarize the recent studies on the pharmacological activities o...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2021.173908
更新日期:2021-01-27 00:00:00
abstract::The aim of the present research was to characterize the pharmacokinetic, pharmacodynamic, and efficacy profiles of alogliptin, a novel quinazolinone-based dipeptidyl peptidase-4 (DPP-4) inhibitor. Alogliptin potently inhibited human DPP-4 in vitro (mean IC(50), ~ 6.9 nM) and exhibited > 10,000-fold selectivity for DPP...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.04.047
更新日期:2008-07-28 00:00:00
abstract::Intracellular accumulation of calcium is thought to play an integral role in the progression of ischemic injury and cell death. We infused the calcium entry blocker, nitrendipine (1.5 micrograms/kg per min), into cats in order to investigate the importance of extracellular Ca2+ influx during hemorrhagic shock. Nitrend...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90510-7
更新日期:1984-01-13 00:00:00
abstract::The effects of intracerebroventricular (i.c.v.) or intravenous (i.v.) administration of morphine on colonic motility were investigated in conscious dogs chronically fitted with a strain gauge transducer sutured to the serosa of the proximal colon. Morphine administered i.v. (100 micrograms/kg) or i.c.v. (10 micrograms...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90479-0
更新日期:1985-10-29 00:00:00
abstract::The effects of THIP and isoguvacine on 3H-flunitrazepam binding to washed membranes prepared from the cerebral cortex of adult rats have been examined. THIP, which has only minimal stimulatory effects on benzodiazepine (BZ) receptor binding, has been found to inhibit the stimulation induced by small concentrations (2 ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(79)90321-2
更新日期:1979-10-15 00:00:00
abstract::Electrophysiological and pharmacological studies have shown that peripheral-type benzodiazepine receptors modulate voltage-sensitive calcium channels in the heart. We have compared these binding sites with binding sites for [3H]dihydropyridines, which are believed to label such channels. Although no direct or alloster...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90291-2
更新日期:1985-12-17 00:00:00