Abstract:
:Donepezil (E2020) is a novel cholinesterase inhibitor for the treatment of Alzheimer's disease. Recent studies show that it may act on targets other than acetylcholinesterase in the brain. In the present study, the actions of donepezil on voltage-gated Na+ and K+ channels were investigated in rat dissociated hippocampal neurons. Donepezil reversibly inhibited voltage-activated Na+ current (I(Na)), delayed rectifier K+ current (I(K)) and fast transient K+ current (I(A)). The inhibition of donepezil on I(Na) was dependent on the holding potential. When neurons were held at -100, -80 and -60 mV, the IC50 value was 436+/-19, 291+/-26 and 3.8+/-0.3 microM, respectively. The drug did not affect the activation, fast inactivation of I(Na) and its recovery from fast inactivation. The inhibition of donepezil on I(K) (IC50=78+/-5 microM) was voltage-dependent, whereas that on I(A) (IC50=249+/-25 microM) was voltage-independent. Donepezil caused a significant hyperpolarizing shift of the voltage-dependence of the activation and steady-state inactivation of I(K), without affecting the kinetic properties of I(A). Due to the high concentrations used, the blocking effects of donepezil on the voltage-gated ion channels are unlikely to contribute to the clinical benefits in patients with Alzheimer's disease.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Yu B,Hu GYdoi
10.1016/j.ejphar.2004.12.004keywords:
subject
Has Abstractpub_date
2005-01-31 00:00:00pages
15-21issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(04)01397-4journal_volume
508pub_type
杂志文章abstract::Specific binding of [3H]imipramine to its recognition sites in frontal cortex and levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) as well as uptake of serotonin by crude synaptosomal (P2) fraction were determined in a group of rats chronically (for 21 days) treated with differen...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90429-8
更新日期:1987-06-19 00:00:00
abstract::Vasodilatory responses to bradykinin (BK) and acetylcholine (ACh) were compared in phenylephrine preconstricted perfused kidneys from 30-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Responses to ACh did not differ between kidneys from SHRSP and WHY. BK-in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90675-t
更新日期:1992-01-14 00:00:00
abstract::The neuroprotective effects of verbascoside, one of phenylpropanoid glucoside isolated from the Chinese herbal medicine Buddleja officinalis Maxim, on 1-methyl-4-phenylpyridinium ion (MPP(+)) induced apoptosis and oxidative stress in PC12 neuronal cells were investigated. Treatment of PC12 cells with MPP(+) for 48 h i...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02240-9
更新日期:2002-09-13 00:00:00
abstract::In rat thoracic aorta, contractile responses to arginine vasopressin are two-fold higher in females than in males. To determine the roles of extracellular and intracellular Ca2+ in this sexual dimorphism in vascular function, vascular reactivity and Ca2+ channel function were examined in thoracic aortae of male and fe...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00700-6
更新日期:1998-11-20 00:00:00
abstract::Previous results indicated that the rabbit could represent a suitable model for investigations on the functional role of alpha 2-adrenoceptors in fat cells, but the characterization of these receptors was not resolved yet. In the present report, imidazoline compounds were used to attempt a better definition of rabbit ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(90)90010-u
更新日期:1990-04-25 00:00:00
abstract::Thapsigargin (TG), an inhibitor of Ca(2+) ATPase pumps in the endoplasmic reticulum (ER), inhibits replication of human vascular smooth muscle cell (hVSMC) at low nM concentrations. TG blocks replication of other cell types through promotion of ER stress (ERS). In order to determine whether ERS may mediate the cytosta...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.05.036
更新日期:2013-08-15 00:00:00
abstract::CPP, administered systemically, elicited four distinct responses characteristic of serotonin-receptor activation in the central nervous system. The crossed extensor reflex in the acutely spinalized rat was enhanced by treatment with CPP, 1-16 mg/kg. CPP, 1.11-10 mg/kg, elicited a dose-related increase in head twitches...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90117-0
更新日期:1977-07-01 00:00:00
abstract::Effects of N-ethylmaleimide or forskolin on electrically evoked dopamine release were investigated in striatal slices of rats pretreated with methamphetamine. N-Ethylmaleimide and forskolin both enhanced the evoked dopamine release in a concentration-dependent manner. The enhancement by N-ethylmaleimide of spontaneous...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90135-x
更新日期:1994-05-23 00:00:00
abstract::Non-peptide antagonists of the NK1 and NK2 receptors were tested as inhibitors of the reaction time in the rat tail-flick and on the decrease of reaction time induced by the intrathecal injection of the NK1 receptor selective agonist [Sar9,Met(O2)11]SP or of the NK2 selective agonist NKA-(4-10). The decrease in reacti...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90782-d
更新日期:1993-03-02 00:00:00
abstract::The mode of binding of [3H]BQ-123 (cyclo(-D-Trp-D-Asp-[prolyl-3,4 (n)-[3H]]Pro-D-Val-Leu)), an endothelin receptor antagonist radioligand, was evaluated in the human neuroblastoma cell line SK-N-MC at 37 degrees C. Scatchard analysis indicated the presence of a single class of [3H]BQ-123 binding sites with a high affi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00670-3
更新日期:1995-02-14 00:00:00
abstract::Low doses of BHT 920, LY 171555 and (+)3PPP, three dopamine agonists selective for D-2 receptors, induced yawning in rats. This effect was reduced by the selective D-1 antagonist SCH 23390 but the antagonism did not exceed a 50% reduction from the control values. In contrast, the selective D-2 antagonist (-)sulpiride ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90162-2
更新日期:1987-02-10 00:00:00
abstract::AY-22,241 (Actodigin) is a new rapid-acting semisynthetic cardiotonic steroid. In experiments on contractility of cat papillary muscle, Actodigin (2 times 10(-7) to 4 times 10(-6) M) produced a dose-dependent positive inotropic effect, a marked increase in the maximum rate of force development, and no change in restin...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(75)90316-7
更新日期:1975-05-01 00:00:00
abstract::The aim of this study was to investigate the effects of chronic lithium treatment on calcium (Ca2+)-stimulated adenylate cyclase activity in rat striatum and hippocampus, and to elucidate the effect of lithium treatment on the neurotransmitter/GTP-mediated inhibition of Ca2+-stimulated enzyme activity in the two brain...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90796-6
更新日期:1989-09-22 00:00:00
abstract::Baicalein, a naturally occurring flavone, has been proved as a promising chemopreventive compound for many chronic human diseases. The aim of this work was to investigate whether treatment with baicalein prevented nonalcoholic steatohepatitis (NASH) induced by methionine-choline-deficient (MCD) diet. Rats were divided...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.06.006
更新日期:2014-09-05 00:00:00
abstract::Galantamine is efficacious for vascular dementia and Alzheimer's disease. Its application leads to some negative gastrointestinal side effects. The present study observes galantamine-induced influence on gastrointestinal motility of rats and its effects on isolated gastrointestinal smooth muscles. The gastrointestinal...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.07.054
更新日期:2004-09-13 00:00:00
abstract::The ability of calcium entry blockers to inhibit allergic histamine release from rabbit leukocytes was studied. Bepridil, verapamil, nifedipine, diltiazem and TMB-8 produced concentration-dependent inhibition of allergic histamine release from rabbit leukocytes. The calculated IC50s (microM) were as follows: verapamil...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90261-4
更新日期:1985-01-08 00:00:00
abstract::Although an inhibition of action potential conduction in nerve fibers possibly contributes to at least a part of antinociception produced by analgesics and the adjuvants, it has not been fully examined yet how the conduction inhibition differs in extent among their drugs. We investigated the effects of various antidep...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.11.047
更新日期:2018-01-15 00:00:00
abstract::Extracellular diadenosine polyphosphates (ApnA) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular ApnA cause alteration of the heart functioning via purine receptors in d...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.12.024
更新日期:2018-02-05 00:00:00
abstract::We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s) in the superficial gray layer of the superior colliculus of rats. These studies showed dense binding of (3-[125I]iodotyrosyl13)-[Ala11,15]Ac-endothelin-1-(6-2 1) (BQ3020) (for endothelin ETB receptors), while tissues incubated with [125I...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00205-2
更新日期:1998-04-17 00:00:00
abstract::Neuropeptides represent by far the most common signalling molecules in the central nervous system. They are involved in a wide range of physiological functions and can act as neurotransmitters, neuromodulators or hormones in the central nervous system and in the periphery. Accumulating evidence during the past 40 year...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2009.09.070
更新日期:2010-01-10 00:00:00
abstract::The paraventricular nucleus of the hypothalamus (PVN) contains dense orexin 2 (OX2) receptor. We examined the mechanisms of OX2 receptor-mediated excitation on electrophysiologically identified type I (putative magnocellular), low-threshold spikes (LTS)-expressing type II (putative preautonomic), and non-LTS type II (...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172802
更新日期:2020-02-15 00:00:00
abstract::In chloralose-anaesthesized cats, clonidine, an alpha 2-adrenoceptor agonist with an imidazole ring, depressed pudendal nerve reflex activity. Clonidine's inhibitory action on this compound action potential response was mimicked by guanabenz, a non-imidazole alpha 2-adrenoceptor agonist, and was reversed by SK & F 864...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90551-z
更新日期:1991-03-26 00:00:00
abstract::The effects of the metabotropic glutamate (mGlu) receptor agonists (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or 1S,3R-ACPD on gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic responses have been investigated in vitro in CA1 pyramidal cells of rat hippocampal slices. Bath application...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00223-8
更新日期:1995-08-04 00:00:00
abstract::Curcumin, main compound obtained from rizhoma of Curcuma longa, shows antitumoral, antioxidant, anticarcinogenic and gastric protective properties. Recently, it has been demonstrated that curcumin exerts its gastric protective action due to an increase in gastric nitric oxide (NO) levels. However, it is unknown whethe...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.02.030
更新日期:2014-05-05 00:00:00
abstract::The effects of conditioned fear on gross activity, heart rate, PQ interval, noradrenaline and adrenaline were studied in freely moving rats. Subcutaneous (s.c.) injections of atropine methyl nitrate (0.5 mg/kg) during rest resulted in a significant shortening of the PQ interval, indicating that the PQ interval can be ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00261-1
更新日期:1998-06-05 00:00:00
abstract::We have investigated the influence of physico-chemical parameters (chemical structure and lipophilicity), biochemical properties (catabolism, affinity for 3H-etorphine binding sites and 3H-(D-Ala)2-Leu5-enkephalin amide binding sites) and biological activity in isolated organs (guinea-pig ileum and mouse vas deferens)...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(80)90114-4
更新日期:1980-04-11 00:00:00
abstract::Effects of two typical neuroleptics haloperidol and loxapine, and an atypical antipsychotic clozapine on excitatory synaptic transmission were examined in the CA1 area of rat hippocampal slices. Haloperidol (10 mumol) and loxapine (10 mumol) increased extracelllar evoked field potentials by an average of 57 and 125% o...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90151-7
更新日期:1993-04-28 00:00:00
abstract::Saturable, high-affinity binding sites for [3H]saxitoxin were identified in equine portal vein smooth muscle membranes. These sites had a dissociation constant of 0.29 nM and a maximal binding capacity of 115 fmol.mg-1 of protein. A similar dissociation constant was obtained with cells prepared from rat portal vein. S...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90624-f
更新日期:1990-08-10 00:00:00
abstract::We previously reported that glycoxidized low-density lipoprotein (glycoxidized LDL) enhanced monocyte chemoattractant protein-1 (MCP-1) mRNA expression through activation of nuclear factor-kappaB (NF-kappaB). Here we investigated the effects of dilazep, an anti-platelet agent, and fenofibric acid, an active metabolite...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)02109-5
更新日期:2003-08-15 00:00:00
abstract::The contractile actions of imidazoline alpha-adrenoceptor agonists were investigated in human vas deferens longitudinal and circular muscle. The effects of phenoxybenzamine were studied in comparison to dibenamine and SZL-49 (4-amino-6,7-dimethoxy-2-quinazolinyl-4-(2-bicyclo[2,2,2]octa-2,5-dienylcarbonyl-2-piperazine)...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01346-3
更新日期:2003-02-21 00:00:00