Abstract:
:The radioligand binding profiles and in vivo pharmacological characteristics of YM-44781, YM-44778 and YM-49598, novel non-peptide tachykinin receptor antagonists, were examined and compared to those of FK-888 and GR-159897. Since no functional NK(3) receptors were found in the rat bladder, the emphasis will be on the other two subtypes. YM-44781 and YM-49598 exhibited high binding affinities at NK(2) (pK(i) = 9.94 +/- 0.03) and NK(1) (pK(i) = 9.09 +/- 0.02) receptors, respectively, whereas YM-44778 exhibited high binding affinities at both NK(1) (pK(i) = 8.08 +/- 0.07) and NK(2) (pK(i) = 8.55 + 0.04) receptors stably transfected in CHO-K1 cells (Chinese hamster ovary cells). In an in vivo rat model, a drug-induced bladder contraction model, antagonism of the contractions produced by the selective NK(2) receptor agonist, [betaAla8]neurokinin A (4-10) (10 microg x kg(-1) i.v.) was observed after intravenous administration (dose range 0.001-1 mg x kg(-1)) of YM-44781 and YM-44778 (IC(50) = 27 +/- 8 and 100 +/- 44 microg x kg(-1), respectively). YM-44781 was more potent (about 3-fold) than YM-44778. YM-49598 was almost inactive but produced a potent inhibition (IC(50) = 11 +/- 7 microg x kg(-1)) of the contraction of the rat urinary bladder induced by challenge with the NK(1)-selective receptor agonist [Sar9,Met(O(2))11]substance P sulphone (0.3 microg x kg(-1)). YM-44781 and YM-44778 did not produce major inhibition of [Sar9,Met(O(2))11]substance P-induced bladder contraction. These findings indicate that YM-44781 and YM-49598 are potent NK(2) and NK(1) receptor antagonists, respectively, whereas YM-44778 is a nonselective NK(2)/NK(1) receptor antagonist in the drug-induced bladder contraction model.
journal_name
Pharmacologyjournal_title
Pharmacologyauthors
Choppin A,Groke G,Bringas A,Stepan G,Dillon MPdoi
10.1159/000056193subject
Has Abstractpub_date
2002-05-01 00:00:00pages
96-102issue
2eissn
0031-7012issn
1423-0313pii
56193journal_volume
65pub_type
杂志文章相关文献
PHARMACOLOGY文献大全abstract:BACKGROUND:Centhaquin is a centrally acting hypotensive drug like clonidine. Clonidine also produces analgesia and hypothermia in mice and potentiates morphine analgesia. Clonidine analgesia is blocked by idazoxan and naloxone while it is potentiated by BQ123 and sulfisoxazole. This study was conducted to determine the...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000331880
更新日期:2011-01-01 00:00:00
abstract::Angiotensin II (ANG II) is a potent vasoconstrictor in most vascular beds. We studied the role of cyclooxygenase products and/or endothelium-derived relaxing factor (EDRF) in modulating the pressor response to ANG II in the isolated, blood perfused dog lung. ANG II was given as a bolus dose of 2, 4 and 8 micrograms be...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000138709
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND/AIMS:In this study, we evaluated the functional impact of facilitatory presynaptic adenosine A2A and muscarinic M1 receptors in the recovery of neuromuscular tetanic depression caused by the blockage of high-affinity choline transporter (HChT) by hemicholinium-3 (HC-3), a condition that mimics a myasthenia-l...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000494058
更新日期:2019-01-01 00:00:00
abstract:OBJECTIVE:To study the myocardial benefit effect and mechanism of paeoniflorin on myocardial ischemia reperfusion injury (MIRI) in rats. METHODS:Hundred SD rats were randomly divided into 5 groups: sham group, model group, Paeoniflorin (15 mg/kg) group, Paeoniflorin (30 mg/kg) group, and Paeoniflorin (60 mg/kg) group....
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000503583
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:Advanced glycation end products (AGEs) play a pivotal role in the initiation and progression of osteoarthritis (OA). Peroxisome proliferator-activated receptor-γ (PPARγ) has been shown to exhibit anti-inflammatory and anticatabolic properties and to be protective in animal models of OA. This study was aimed t...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000369074
更新日期:2014-01-01 00:00:00
abstract::The effect of cimetidine and two new histamine H2-receptor antagonists, oxmetidine and SKF 93479, on histamine-stimulated adenylate cyclase activity was studied in guinea pig gastric mucosal cells. Histamine stimulated the enzyme activity in concentration-dependent fashion. The concentration-response curve of histamin...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000137973
更新日期:1984-01-01 00:00:00
abstract::The dependence of intestinal absorption of xenobiotics on the blood flow rate increases from blood flow independent to blood flow limited absorption as the absorbability of the substances increases. Since the absorbed substances are mainly drained by the blood flowing through the subepithelial vessels, not only the to...
journal_title:Pharmacology
pub_type: 杂志文章,评审
doi:10.1159/000137409
更新日期:1980-01-01 00:00:00
abstract:OBJECTIVE:The primary aim of the present investigation was to determine and compare the pharmacokinetic (PK) profiles of inorganic phosphate in serum and urine after intravenous administration of sodium glycerophosphate and inorganic sodium phosphate. Additionally, study product safety profiles were evaluated. SUBJECT...
journal_title:Pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1159/000331341
更新日期:2011-01-01 00:00:00
abstract::Topically unilaterally applied lisuride caused dose-related lowering of intraocular pressure in ipsilateral (treated) but not in contralateral eyes of normal rabbits. The ocular hypotensive response induced by lisuride was antagonized by pretreatment with metoclopramide, a dopamine receptor antagonist, and was partial...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000028249
更新日期:1998-11-01 00:00:00
abstract::The pregnane X receptor (PXR/NR1I2) gene is a master regulator for a number of cytochrome P450s (CYPs) and drug transporters. This study aimed to detect the single nucleotide polymorphisms (SNPs) of the PXR gene in Han Chinese (n = 186) and to compare the frequencies of polymorphisms of the PXR gene with those in Cauc...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000123687
更新日期:2008-01-01 00:00:00
abstract::Previously published data from this laboratory on the urinary excretion of 3-hydroxymethyl antipyrine (one of the major metabolites of antipyrine in man) have to be reconsidered, because of use of an impure reference substance in the high-pressure liquid chromatographic assay method. Comparison with newly synthesized,...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000137594
更新日期:1982-01-01 00:00:00
abstract::We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4-fluorobenzyl]-5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl]amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The o...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000455916
更新日期:2017-01-01 00:00:00
abstract::This study was performed to investigate the effect of muscimol on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity as measured in mice, and the morphine-induced hyperactivity was inhibited dose-depen...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000064345
更新日期:2002-08-01 00:00:00
abstract::The present study was designed to investigate the effects of fluid administration on survival in endotoxemic or septicemic male Sprague-Dawley rats. Endotoxemia was induced by intravenous injection of Escherichia coli lipopolysaccharide (LPS), and septicemia produced by cecal ligation and puncture (CLP). In endotoxemi...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000139053
更新日期:1993-05-01 00:00:00
abstract::The systemic and coronary hemodynamic effects of the nitrovasodilator, pirsidomine, were compared with SIN-1, nitroprusside, and nitroglycerin. Four groups consisting of 32 experiments were performed in 17 conscious dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000139372
更新日期:1996-02-01 00:00:00
abstract::Exposure of rat portal veins to an N2-gassed buffer markedly increased 86Rb outflow. Moreover, glucose caused a pronounced reduction in 86Rb outflow from portal veins perfused with an N2-gassed buffer. Pinacidil, cromakalim and diazoxide provoked a sustained increase in 86Rb outflow. The stimulatory effect of pinacidi...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000138878
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND/AIMS:In the present study, we tested whether or not acute antioxidant treatment with vitamin C is able to protect the heart during myocardial infarction. The effects of vitamin C on the autonomic balancing of the heart and on the histopathological and immunohistochemical changes in response to isoproterenol ...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000222245
更新日期:2009-01-01 00:00:00
abstract::Erythropoietin (EPO) has been used for the management of renal anemia. Recent studies suggest the pleiotropic properties of EPO in various tissues such as brain, kidney and vasculature. Diabetes mellitus is a major risk for development of vascular impairment. The aim of the present study was to investigate the hypothe...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000343963
更新日期:2013-01-01 00:00:00
abstract::Using the method of staining mucus with Alcian blue and destaining it with magnesium chloride, it was found that intragastric administration of carbenoxolone in mice did not significantly affect duodenal mucus synthesis at doses which remarkably increased gastric mucus synthesis. However, in vitro study showed that ca...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000138201
更新日期:1986-01-01 00:00:00
abstract:AIM:Our study aimed to investigate the effect of amlodipine on bone metabolism in orchidectomized rats. METHODS:Eight-week-old rats were divided into three groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group a...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000335491
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Angiogenesis is usually driven by inflammation. Matrix metalloproteinases MMP-3 and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 are implicated in vascular remodeling. TIMP-2 exhibits antiangiogenic properties. Statins show benefits that are additional to lipid lowering including pro- ...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000360860
更新日期:2014-01-01 00:00:00
abstract::Oxygen radicals have been considered to be important regulatory molecules in Helicobacter pylori-induced gastric ulceration and carcinogenesis. H. pylori-induced inflammation has been shown to be associated with cyclooxygenase-2 (COX-2) expression in experimental animals and human patients. This study aimed to determi...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000065532
更新日期:2002-12-01 00:00:00
abstract:INTRODUCTION:Although it is beneficial to protect the skin from natural aging, especially in an aging society, the approach by which this can be achieved is still not well known. Hochu-ekki-to, a Chinese natural medicine, has various advantageous effects; however, there is no report about its influence on skin aging. ...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000504985
更新日期:2020-01-01 00:00:00
abstract::The frequent resistance of malignant tumors to chemotherapy documents the fact that numerous patients are uselessly traumatized by highly toxic drugs. Investigations into this resistance have shown that many different mechanisms exist which can abolish the antitumor action of chemotherapeutics. So far, no safe method ...
journal_title:Pharmacology
pub_type: 杂志文章,评审
doi:10.1159/000112864
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to evaluate the efficacy, tolerability, and safety of once-a day trazodone tablets (Trittico Prolong® 300 mg) in patients with moderate to severe depression in routine clinical practice. METHODS:Men and women ≥18 years old with Montgomery-Åsberg Depression Rating Scale (MADRS) scores...
journal_title:Pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1159/000492079
更新日期:2018-01-01 00:00:00
abstract::Nitric oxide has been shown to decrease myocardial contractility and O2 consumption. This study was designed to evaluate the hypothesis that nitric oxide-mediated increases in cyclic GMP require elevated cyclic AMP to produce cardiac depression. Using isolated, Langendorff-perfused rat hearts, we determined the effect...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000139529
更新日期:1997-10-01 00:00:00
abstract::This study tests the hypothesis that contractile responses in aortae of hypertensive rats are more dependent on gap junctional communication compared to those from normotensive rats. The experimental approach was pharmacological, using inhibitors of gap junctional activity (heptanol and octanol). Two models of experim...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000056069
更新日期:2001-01-01 00:00:00
abstract::The calcium channel antagonist, nifedipine (0.1 microM), only slightly inhibited the response to the full alpha 1-adrenoceptor agonist, (-)-norepinephrine, in rat aorta, but nearly completely inhibited the response to the partial alpha 1-adrenoceptor agonist, (-)-dobutamine, indicating that (-)-norepinephrine primaril...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000138906
更新日期:1992-01-01 00:00:00
abstract::Three doses (0.31, 3.1 and 31 mg/kg) of methotrexate (MTX) were given intravenously to rats. The resulting concentration-time curves in plasma (normalized by dividing the plasma concentration by a multiple of the dose) were not superimposable, indicating nonlinear plasma pharmacokinetics. In liver, kidney, bone marrow...
journal_title:Pharmacology
pub_type: 杂志文章
doi:10.1159/000137723
更新日期:1982-01-01 00:00:00
abstract::Gene knockout mice have proven to be very useful in understanding the role of xenobiotic-metabolizing enzymes in chemical toxicity and carcinogenesis. The combination of gene knockout technology with transgenic mouse technology should provide more versatile and suitable animal models to study the risks of chemical exp...
journal_title:Pharmacology
pub_type: 杂志文章,评审
doi:10.1159/000028395
更新日期:2000-09-01 00:00:00