Abstract：
:In strips of pig coronary arteries incubated in oxygenated Krebs-bicarbonate solution at 37 degrees C, dotarizine blocked the phasic contractions evoked by 5-HT (0.5 microM) or K+ depolarization (35 mM K+) with an IC50 of 0.22 and 3.7 microM, respectively. Flunarizine inhibited both types of contractions with IC50 values of 1.7 microM for 5-HT and 2.4 microM for K+ responses. In Xenopus oocytes injected with in vitro transcribed RNA encoding for 5-HT2A or 5-HT2C receptors, 5-HT (100 nM for 20 s) applied every 10 min caused, in both cases, a reproducible inward current through Ca2(+)-activated Cl- channels (ICl). Dotarizine inhibited the 5-HT2A response in a concentration-dependent manner, with an IC50 of 2.2 nM. In contrast, the 5-HT2C response was unaffected by 1 microM dotarizine and blocked around 62% by 10 microM of this drug. The ICl activated either by intracellular injection of inositol 1,4,5-trisphosphate (IP3) in oocytes or by direct photorelease of Ca2+ in DM-nitrophen-injected oocytes was unaffected by 10 microM dotarizine. It is concluded that dotarizine blocks 5-HT2A receptors with a high affinity; the compound is devoid of intracellular effects on any further steps of the transduction pathway (i.e., IP3 receptor). Contrary to flunarizine that blocks equally well the serotonergic and the K+ vascular responses, dotarizine exhibits 17-fold higher affinity for vascular 5-HT receptors. These findings might be relevant to an understanding of the mechanism involved in the use of dotarizine and flunarizine as prophylactic agents in migraine.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Montiel C,Herrero CJ,García-Palomero E,Renart J,García AG,Lomax RBdoi
10.1016/s0014-2999(97)01073-xsubject
Has Abstractpub_date
1997-08-06 00:00:00pages
183-93issue
2eissn
0014-2999issn
1879-0712pii
S0014-2999(97)01073-Xjournal_volume
332pub_type
杂志文章abstract：:Serotonin 1A receptor agonists have attracted much interest recently as potential therapeutic agents for levodopa-induced motor complications, such as dyskinesia and motor fluctuations. The effects of piclozotan (SUN N4057) on a rat model of advanced Parkinson's disease were investigated. Parkinsonian rats, unilateral...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.09.013
更新日期：2010-12-15 00:00:00
abstract：:Previous studies have shown that sertindole (1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl]ethyl ]-2 imidazolidinone), an atypical antipsychotic drug that is a potent 5-HT2A and dopamine D2 receptor antagonist, preferentially affects mesocorticolimbic rather than mesostriatal dopamine neurons. Usin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00936-4
更新日期：1999-02-12 00:00:00
abstract：:The effect of apomorphine (ap) was investigated in rats kept in a familiar cage; 0.25-5 mg/kg s.c. produced a short-lasting, abnormal hypermotility consisting mainly of locomotion and sniffing without grooming. Ap was administered to rate pretreated s.c. with various drugs. Ap hypermotility was antagonized by 12 neuro...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90092-3
更新日期：1976-04-01 00:00:00
abstract：:Nitric oxide (NO) plays an important role in the cytotoxic activity of macrophages towards tumour cells and microbial pathogens. We investigated whether alteration of intracellular thiol levels modulates the cytotoxic effects of different NO donors and lipopolysaccharide-induced NO in the murine macrophage cell lin J7...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00918-1
更新日期：1997-02-19 00:00:00
abstract：:We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90737-o
更新日期：1992-09-22 00:00:00
abstract：:Direct instillation of a recombinant human form of MMP-12 (rhMMP-12) in mice airways elicited an early inflammatory response characterized by neutrophil influx, cytokine release and gelatinase activation followed by a delayed response, mainly characterized by macrophage recruitment. As this experimental model of lung ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.11.070
更新日期：2007-03-15 00:00:00
abstract：:Concentration-relaxation curves for pinacidil and cromakalim were obtained in isolated guinea-pig tracheas contracted by histamine. Pinacidil produced complete relaxation with an EC50 value of 2.8 microM. The antidiabetic sulfonylurea, glibenclamide (0.1, 1, 10 microM), caused concentration-dependent rightward shifts ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90312-t
更新日期：1990-05-16 00:00:00
abstract：:Inflammation, closely associated with obesity, is emerging as an important risk factor for the pathophysiological development of atherosclerosis and diabetes mellitus. Fat balance is critical in the aetiology of obesity. Lipoprotein lipase is an important enzyme in lipid metabolism. The aim of this study was to invest...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.04.032
更新日期：2006-07-01 00:00:00
abstract：:The beta 1- and beta 2-adrenoceptor agonist and thromboxane A2 (TXA2) antagonist properties of trimetoquinol (TMQ, I) and 1-benzyl substituted TMQ analogues [3'-iodo-4',5'-dimethoxy TMQ, II; 3',5'-diiodo-4'-dimethoxy TMQ, III; 3',4'-dimethoxy-5'-nitro TMQ, IV; 3',4'-dimethoxy-5'-amino TMQ; V; and 3',4'-dimethoxy TMQ, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90663-q
更新日期：1990-08-02 00:00:00
abstract：:In Alzheimer's disease (AD), a decline in function of neural progenitor cells (NPCs) results in a reduced capacity for neural regeneration. It has been shown that plasma oxidized low-density lipoprotein (ox-LDL) levels are positively correlated with severity in patients with AD. However, the direct effects of ox-LDL o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173456
更新日期：2020-12-05 00:00:00
abstract：:Ouabain- and bumetanide-resistant potassium fluxes were measured in human erythrocytes incubated in a medium containing calcium and a calcium ionophore. Pharmacological concentrations of rat atrial natriuretic peptide stimulated these fluxes. Although human erythrocytes lack atrial natriuretic peptide receptors, our r...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90082-4
更新日期：1989-07-18 00:00:00
abstract：:Hydrogen sulfide (H2S) is a gaseous molecule and is endogenously produced in the brain by cystathionine beta-synthase, 3-mercaptopyruvate-sulfurtransferase, cysteine aminotransferase and cystathionine γ-lyase. Physiologically, H2S acts as a neuromodulator and regulates synaptic activity of neurons and glia to promote ...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2019.01.072
更新日期：2019-04-15 00:00:00
abstract：:The biological activity of two galanin (GAL) fragments, GAL-(1-16) and GAL-(17-29), was tested in vivo by using a spinal nociceptive flexor reflex model in the rat. Intrathecal (i.t.) GAL-(1-16) had a similar biphasic effect on the flexor reflex, with facilitation at lower doses and facilitation followed by depression...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90502-w
更新日期：1990-06-21 00:00:00
abstract：:HgCl2 and mersalyl increased and later decreased both the spontaneous and evoked transmitter liberation at the frog neuromuscular junction. Lower concentration of HgCl2 exhibited only an inhibitory effect on transmitter release. These mercurials inhibited calcium transport of mitochondria and synaptosomal vesicles. Lo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90438-7
更新日期：1978-10-15 00:00:00
abstract：:Agonists of adenosine A1 receptors have been frequently proposed as candidates for clinical development in treatment of cerebral ischemia and stroke. Numerous experimental studies have shown that pre- and postischemic administration of these drugs results in a very significant reduction of postischemic brain damage. H...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00101-x
更新日期：1996-04-29 00:00:00
abstract：:Although initial resuscitation from cardiac arrest (CA) has increased over the past years, long term survival rates remain dismal. Epinephrine is the vasopressor of choice in the treatment of CA. However, its efficacy has been questioned, as it has no apparent benefits for long-term survival or favorable neurologic out...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2014.06.024
更新日期：2014-10-05 00:00:00
abstract：:The antagonistic effects of a new inositol phosphate derivative, D-myoinositol-1,2,6-trisphosphate (PP56), on pressor responses to preganglionic sympathetic nerve stimulation and exogenously administered phenylephrine or neuropeptide Y (NPY) were investigated in vivo in the pithed rat. In this model an intravenous (i....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90853-i
更新日期：1991-11-12 00:00:00
abstract：:The present paper describes a theoretical study on the mechanism underlying the reaction of cellular glutathione (GSH) with polyunsaturated fatty acid ozonides. The reaction can be catalyzed by glutathione S-transferases and leads to detoxication of the ozonides. Semi-empirical molecular orbital computer calculations ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(92)90031-7
更新日期：1992-12-01 00:00:00
abstract：:Seroma formation is one of the most common complications following breast cancer surgery. It may lead to delay of adjuvant therapies and increasement of therapy costs. Bleomycin sulfate is a sclerosing antibiotic with antineoplastic efficacy. It is locally used in the treatment of pleural effusion. The present study a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.10.067
更新日期：2014-01-15 00:00:00
abstract：:The amyloid precursor protein (APP) has been mainly studied in its role in the production of amyloid β peptides (Aβ), because Aβ deposition is a hallmark of Alzheimer's disease. Although several studies suggest APP has physiological functions, it is still controversial. We previously reported that APP increased glial ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.09.015
更新日期：2011-01-10 00:00:00
abstract：:Vervet monkeys were pharmacologically treated acutely and with repeated dose loading to alter serotonergic systems to assess the role of serotonin in the regulation of the hypothalamus-pituitary-thyroid axis. Acute L-tryptophan administration failed to alter basal levels of thyroid hormones but did decrease the TRH-in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90509-9
更新日期：1980-10-17 00:00:00
abstract：:Prostaglandin E2 increases bradykinin-induced spike activity from polymodal nociceptors of the skin and deep tissues in animals, suggesting sensitization of these receptors. To see whether these neurophysiological observations in animals correspond with increased pain intensity in humans, and whether also vascular noc...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00575-7
更新日期：1995-12-29 00:00:00
abstract：:Molecular mechanisms responsible for diabetes-induced testicular dysfunction are not well understood. This study investigated oxidative stress, stage-dependent DNA base modification and expression of poly (ADP ribose) polymerase 1 (PARP1) in the testes of streptozotocin-induced diabetic rats. Hyperglycemia led to test...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.05.005
更新日期：2014-08-15 00:00:00
abstract：:The present study was undertaken to investigate vascular function in hypercholesterolemic rabbits and also to characterize the effects of pioglitazone on it. Rabbits were fed normal, 0.5% cholesterol chow, or 0.5% cholesterol chow plus 300 ppm pioglitazone for 5 or 10 weeks. The tension of isolated renal artery rings ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.06.062
更新日期：2004-08-30 00:00:00
abstract：:The effects of 2,3-butanedione monoxime (BDM) and 5-[1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydro-6-quinolyl]-6-me thy l-3,6-dihydro-2H-1,3,4-thiadiazin-2-one (EMD 53998) on cardiac muscle were studied in skinned muscle fibres from the right ventricle of the porcine heart. BDM decreases the Ca2+ sensitivity (pCa50 for ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00819-5
更新日期：1996-02-05 00:00:00
abstract：:Depression and cocaine use disorder represent frequent co-current diagnoses and the GABAB receptors are involved in both conditions. This research involved the application of the animal model of depression (bulbectomy, OBX) and cocaine use disorder (self-administration) to assess the efficiency of GABAB receptor agoni...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173324
更新日期：2020-09-15 00:00:00
abstract：:The autoradiographic distribution of putative brain adrenomedullin receptors was investigated using [125I]human adrenomedullin(13-52) as a new radioligand. Specific [125I]human adrenomedullin(13-52) binding sites were very discretely distributed in the rat brain with enrichment seen in the choroid plexus and linings o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01021-4
更新日期：2001-06-08 00:00:00
abstract：:Vascular smooth muscle cell migration to the intima from the media and proliferation in the intima play key roles in atherosclerosis and restenosis after coronary angioplasty. Histamine released from adherent platelets at the injured artery and from mast cells in atheromas has stimulant actions on both smooth muscle c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00716-x
更新日期：1998-11-27 00:00:00
abstract：:The effects of the enantiomers of clenbuterol were compared in four psychopharmacological tests in which beta-adrenergic agonists are known to be active. In mice (+/-)-clenbuterol 0.06 mg/kg decreased motor activity and antagonized the hypothermia induced by 16 mg/kg of apomorphine; at 0.5 mg/kg it increased head-twit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90481-9
更新日期：1985-10-29 00:00:00
abstract：:We investigated the effects of 7-nitroindazole, a specific inhibitor of neuronal nitric oxide (NO) synthase, on NO concentration and on blood flow in rat hippocampus after transient forebrain ischemia which was induced by 4-vessel occlusion for 10 min. NO concentration was measured directly by an NO-selective electrod...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00555-5
更新日期：1999-09-10 00:00:00
