Abstract:
:Lithium, commonly used to treat bipolar disorder, potentiates the ability of the muscarinic agonist pilocarpine to induce seizures in rodents. As this potentiation by lithium is reversed by the administration of myo-inositol, the potentiation may be mediated by inhibition of inositol monophosphatase (IMPase), a known target of lithium. Recently, we demonstrated that ebselen is a 'lithium mimetic' in regard to behaviours in both mice and man. Ebselen inhibits IMPase in vitro and lowers myo-inositol in vivo in the brains of mice and men, making ebselen the only known inhibitor of IMPase, other than lithium, that penetrates the blood-brain barrier. Our objective was to determine the effects of ebselen on sensitization to pilocarpine-induced seizures and neural activity. We administered ebselen at different doses and time intervals to mice, followed by injection of a sub-seizure dose of pilocarpine. We assessed seizure and neural activity by a subjective seizure rating scale, by monitoring tremors, and by induction of the immediate early gene c-fos. In contrast to lithium, ebselen did not potentiate the ability of pilocarpine to induce seizures. Unexpectedly, ebselen inhibited pilocarpine-induced tremor as well as pilocarpine-induced increases in c-fos mRNA levels. Both lithium and ebselen inhibit a common target, IMPase, but only lithium potentiates pilocarpine-induced seizures, consistent with their polypharmacology at diverse molecular targets. We conclude that ebselen does not potentiate pilocarpine-induced seizures and instead, reduces pilocarpine-mediated neural activation. This lack of potentiation of muscarinic sensitization may be one reason for the lack of side-effects observed with ebselen treatment clinically.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Singh N,Serres F,Toker L,Sade Y,Blackburn V,Batra AS,Saiardi A,Agam G,Belmaker RH,Sharp T,Vasudevan SR,Churchill GCdoi
10.1016/j.ejphar.2020.173377subject
Has Abstractpub_date
2020-09-15 00:00:00pages
173377eissn
0014-2999issn
1879-0712pii
S0014-2999(20)30469-6journal_volume
883pub_type
杂志文章abstract::Electrical field stimulation of the isolated adventitial and intima-medial layers of rabbit aorta preloaded with 3H-noradrenaline elicited a 3H outflow. The initial 3H outflow from adventitia was independent of external Ca2+ concentration. Each of the subsequent 3H outflows was mainly Ca2+ sensitive. All stimulation-i...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(76)90156-4
更新日期:1976-10-01 00:00:00
abstract::Carbamazepine moderately depressed the input fiber volley resulting in attenuation of the dendritic epsp and the population spike in CA1 of rat hippocampal slices with a threshold concentration of 20 microM. The depressant effect on the population spike was not antagonized by the adenosine receptor blocker caffeine. P...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90030-5
更新日期:1985-03-26 00:00:00
abstract::Male mice from 14 strains were injected i.p. with tremorine (3.0 mg/kg) or oxotremorine (0.15 or 0.1 mg/kg). Large inter-strain differences in the degree and duration of the subsequent hypothermia were noted. 2 strains, BALB/c and Simpson, were particularly sensitive to the hypothermic effect of oxotremorine. The offs...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(78)90226-1
更新日期:1978-05-01 00:00:00
abstract::Endogenous hydrogen sulfide is produced by cystathionine-γ-lyase and cystathionine-β-synthase in a variety of tissues and has recently been implicated in the regulation of cardiac functions. Acceleration of the heart rate in response to catecholamines is impaired in patients with cirrhosis. The present study was aimed...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.09.039
更新日期:2012-12-05 00:00:00
abstract::The effects of indapamide on contractile responses in various isolated artery rings and on spontaneous mechanical activity in portal vein segments were investigated. Arteries used were: rabbit aorta, mesenteric (fifth branch), femoral and basilar, and sheep coronary arteries. 45Ca2+ uptake was also analysed in rabbit ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90630-z
更新日期:1993-11-30 00:00:00
abstract::Neurotrophic and neuroprotective properties of Hsp70 were studied in olfactory cortex slices of hypertensive rats under normal conditions and under influence of autologous blood (blood clot). Under normal conditions, synaptic response in slices depended on Hsp70 amount in medium. Incubation of slices with Hsp70 showed...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.12.004
更新日期:2012-02-29 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::Vascular hypertrophy occurs during chronic hypertension and contributes to the elevation of peripheral vascular resistance in hypertension. In this study, we examined whether acute pressure overloading of the vascular wall produces activation of mitogen-activated protein (MAP) kinases, enzymes believed to be involved ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00072-8
更新日期:2000-03-17 00:00:00
abstract::The pathophysiology of chronic neurodegenerative diseases, as Alzheimer's diseases, has remained inaccessible till recently. But this situation is changing quickly. In the past decades, genes causing familiar forms of the disease have been identified and provided the genetic framework for the emerging amyloid hypothes...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2009.10.020
更新日期:2010-01-10 00:00:00
abstract::It has been previously demonstrated that selegiline, an irreversible monoamine oxidase B (MAO-B) inhibitor, potentiates glial reaction to injury and possesses some 'trophic-like' activities which do not depend on the inhibition of MAO-B and which are probably associated with the induction of astrocyte-derived neurotro...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(96)00593-6
更新日期:1996-11-07 00:00:00
abstract::The alpha 1-adrenoceptor agonist, SDZ NVI-085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4- methyl-9-(methylthio)-2H-naphth[2,3-b]-1,4-oxazine.HCl; 1 mg/kg i.p.), decreased body temperature of guinea-pigs. Two 5-HT1D receptor antagonists, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00526-q
更新日期:1995-10-24 00:00:00
abstract::It was previously shown that haloperidol, but not clozapine, induced intense rat catalepsy when co-administered with delta-9-tetrahydrocannabinol. The present study investigated whether similar alterations could be observed on striatal c-Fos immunoreactivity after administration of the same drug combinations. Western ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.08.020
更新日期:2008-11-19 00:00:00
abstract::The functional role of metabotropic glutamate (mGlu) receptors in the rat dentate gyrus was investigated. By using extracellular recording techniques in slices, it was found that the depression induced by the mGlu receptor agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylate (ACPD) was mediated through the mGlu grou...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00560-9
更新日期:1995-12-29 00:00:00
abstract::Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, is found in the central nervous system as well as in the heart. CGRP shows high sequence homology with amylin, salmon calcitonin, and adrenomedullin. This study aimed to investigate the effect of CGRP on atrial hemodynamics and atrial natriuretic pe...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.10.020
更新日期:2004-01-12 00:00:00
abstract::To investigate cellular electrophysiologic alterations due to lipid peroxidation of the cell membrane by free radicals as a possible cause of coronary reperfusion arrhythmias, we studied the effects of t-butyl hydroperoxide on the spontaneous action potential and membrane currents of the rabbit sinoatrial and atrioven...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0926-6917(95)90027-6
更新日期:1995-03-16 00:00:00
abstract::Alterations in iron homeostasis are well described in obese patients. The effects of iron chelators on adipose tissue and other organs affected by obesity have been the interest of experimental studies, both in vivo and in vitro. The aim of this review was to update the available information indicating the potential o...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2019.172614
更新日期:2019-10-15 00:00:00
abstract::Nicotine is one of the most representative components in cigarette smoke leading to gastric ulceration. Both ornithine decarboxylase and potassium ion (K(+)) channels are essential for cell growth and wound repair. The aim of the present study is to elucidate the causative relationship of these two factors during woun...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)01610-2
更新日期:2002-05-24 00:00:00
abstract::The nicotinic acetylcholine receptors in the rat stomach were characterized by means of a radioligand binding assay with (-)-[3H]nicotine as ligand. Saturation binding studies on the gastric fundus membranes revealed the presence of two binding sites with dissociation constant (KD) values of 3.1 and 289 nM, and maximu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90490-6
更新日期:1988-01-27 00:00:00
abstract::The anti-cancer effects of dioscin have been widely reported. However, its effect on laryngeal cancer remains unknown. In the present paper, our results showed that dioscin markedly caused cell apoptosis and DNA damage, increased reactive oxygen species (ROS) level, induced S-phase arrest, and inhibited invasion of hu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.02.009
更新日期:2016-03-05 00:00:00
abstract::The effect of simultaneous topical application of adrenergic agonists was investigated on the polydipsia caused by direct carbachol (CCh) stimulation of the rat brain. In addition, fluid selection (4-choice arrangement) was studied. Noradrenaline and isoprenaline fully antagonized the CCh effect after either intracere...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90342-3
更新日期:1981-10-15 00:00:00
abstract::Salvianolic acid B (SalB) is a polyphenolic compound found in Salvia miltiorrhiza Bunge that has several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether SalB has neuroprotective effects in an amyloid β (Aβ) peptide-induced Alzheimer's disease mouse model. Mice were injected ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.02.015
更新日期:2013-03-15 00:00:00
abstract::Inflammatory bowel disease (IBD) is characterized by chronic, recurring inflammation of the digestive tract. Current therapeutic approaches are limited and include biologics and steroids such as anti-TNFα monoclonal antibodies and corticosteroids, respectively. Significant adverse drug effects can occur for chronic us...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.03.038
更新日期:2019-06-05 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::I.v. administration of McN-2378 appeared to preferentially increase cerebral blood flow as opposed to systemic (femoral) blood flow in two strains of monkeys. This cerebral vasodilation was not affected by theta-adrenergic blockade. In the anesthetized dog, the compound transiently lowered systemic arterial pressure w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(75)90209-5
更新日期:1975-01-01 00:00:00
abstract::Neuropathic pain has been suggested to be resistant to treatment with opiates. Such perceived lack of opioid responsiveness may be due to the dose-range over which specific opioid compounds have been studied as well as the efficacy of these compounds. Dihydroetorphine is a novel opiate that demonstrates significantly ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00531-7
更新日期:1998-09-11 00:00:00
abstract::The effects of paxilline, a mycotoxin, on whole-cell outward currents from freshly isolated cells of the rat mesenteric artery were studied. Paxilline inhibited a component of the outward current that was also sensitive to iberiotoxin. Inhibition could be observed at a concentration of 10 nM and complete inhibition of...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00188-0
更新日期:1999-05-07 00:00:00
abstract::In rats, tolerance to the analgesic effect of intraventricular substance P (SP) develops quickly. In rats made tolerant to [D-Ala2, D-Leu5]enkephalin the analgesic efficacy of SP is reduced significantly. The latter result suggests some overlap in the sites of action of SP and [D-Ala2,D-Leu5] enkephalin. Since SP seem...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90119-5
更新日期:1984-02-10 00:00:00
abstract::Nicotine produced antinociception in mice which was antagonized noncompetitively by naloxone. In addition, at significantly lower doses, nicotine noncompetitively antagonized morphine-induced antinociception. A speculative suggestion regarding the opiatergic and anti-opiatergic actions of nicotine is that it significa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0926-6917(93)90009-f
更新日期:1993-12-01 00:00:00
abstract::In the present study, we reported the metabolic effects of salidroside, one of the active components of Rhodiola Rosea, on skeletal muscle cells. Salidroside dose-dependently stimulated glucose uptake in differentiated L6 rat myoblast cells. Inhibitor of AMP-activated protein kinase (AMPK) by pretreating the cells wit...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.04.036
更新日期:2008-07-07 00:00:00
abstract::We have investigated the mode of cardiovascular action of the stimulant methylhexaneamine (MHA) in terms of direct or indirect adrenergic actions in anaesthetised rats. Male and female rats were anaesthetised with pentobarbitone and pressor (changes in diastolic blood pressure) and cardioaccelerator responses to MHA w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.10.047
更新日期:2019-01-15 00:00:00