Inhibitory effects of trimetazidine dihydrochloride on aggregation, serotonin release and malondialdehyde production in rabbit platelets.
スポンサーリンク
概要
- 論文の詳細を見る
Aggregation, serotonin release and malondialdehyde (MDA) production via cyclooxygenase and thromboxane A<SUB>2</SUB> synthetase were investigated in rabbit platelets. Trimetazidine dihydrochloride (TMZ) attenuated the collagen-induced aggregation more strongly than the arachidonic acid (AA)-, thromboxane A<SUB>2</SUB> agonist (U-46619)-, Ca<SUB>2+</SUB>-ionophore (A-23187)- and ADP-induced aggregation: IC50 values were 1.0±0.1, 4.4±0.3, 4.3±0.4, 4.1±0.7 and 3.3±0.2 mM, respectively. TMZ decreased dose-dependently the serotonin release induced by collagen and A-23187, but did not decrease that induced by AA. TMZ also decreased the MDA production induced by collagen and A-23187 (IC50: 0.3±0.03 and 1.0±0.1 mM, respectively), but did not decrease the production induced by AA. Furthermore, TMZ decreased dose-dependently the MDA production induced by exogenous phospholipase A<SUB>2</SUB>. On the other hand, indomethacin (10 μM) attenuated the aggregations induced by collagen and AA, but not by the other agents, and decreased the serotonin release and the MDA production induced by collagen, A-23187 and AA. The present results suggest that TMZ may inhibit the process preceding the cyclooxygenase pathway in the AA cascade, and subsequently may attenuate the aggregation and the serotonin release via thromboxane A<SUB>2</SUB> production from endogenous AA.
- 公益社団法人 日本薬理学会の論文
著者
-
Shirahase Hiroaki
Research Laboratories Kyoto Pharmaceutical Company Ltd.
-
Kakeya Nobuharu
Research Laboratories Kyoto Pharmaceutical Industries
-
OSUMI Seimei
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
-
KURAHASHI Kazuyoshi
Department of Pharmacology, Faculty of Medicine, and Radioisotope Research Center
-
SUZUKI Yukiko
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
関連論文
- Novel Tetrahydroisoquinoline Derivatives with Inhibitory Activities against Acyl-CoA: Cholesterol Acyltransferase and Lipid Peroxidation
- Novel Acyl-CoA: Cholesterol Acyltransferase Inhibitor: Indoline-Based Sulfamide Derivatives with Low Lipophilicity and Protein Binding Ratio
- A Novel Series of Thromboxane A_2 Synthetase Inhibitors with Free Radical Scavenging and Anti-peroxidative Activities
- Bioavailable Acyl-CoA : Cholesterol Acyltransferase Inhibitor with Anti-peroxidative Activity : Synthesis and Biological Activity of Novel Indolinyl Amide and Urea Derivatives
- Inhibitory Effect of Acyl-CoA : Cholesterol Acyltransferase Inhibitor-Low Density Lipoprotein Complex on Experimental Atherosclerosis(Biopharmacy)
- Synthesis and Biological Evaluation of (S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acids : A Novel Series of PPARγ Agonists
- AS-924, a Novel Bifunctional Prodrug of Ceftizoxime
- Characteristics of 1,3-Bis-(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy) propane Dihydrochloride (N-556), a Prodrug for the Oral Delivery of Disodium Cromoglycate, in Absorption and Excretion in Rats and Rabbits
- PRODRUGS FOR THE ORAL DELIVERY OF DISODIUM CROMOGLYCATE (DSCG)
- STRUCTURE-ORAL ABSORPTION RELATIONSHIP OF NEW ORALLY ACTIVE CEPHALOSPORIN ESTERS, CEFCANEL DALOXATE AND THE RELATED COMPOUNDS
- Effects of Cholesterol Diet on Vasculopathy and Nephropathy in Salt-loaded Dahl-S Rats(Circulatory system, Proceedings of the 32nd Annual Meeting)
- Effect of Topically Applied Iganidipine Dihydrochloride, a Novel Calcium Antagonist, on Optic Nerve Head Circulation in Rabbits
- 2-Acyl-tetrahydroisoquinoline-3-carboxylic Acids: Lead Compounds with Triple Actions, Peroxisome Proliferator-Activated Receptor α/γ Agonist and Protein-Tyrosine Phosphatase 1B Inhibitory Activities
- A Novel Series of (S)-2,7-Substituted-1,2,3,4-tetrahydroisoquinoline-3-carboxylic Acids: Peroxisome Proliferator-Activated Receptor α/γ Dual Agonists with Protein-Tyrosine Phosphatase 1B Inhibitory Activity
- EFFECTS OF C-TERMINAL OCTAPEPTIDE OF CHOLECYSTOKININ AND PROSTAGLANDINS ON ADRENERGIC FUNCTIONS IN THE GUINEA-PIG GALLBLADDER AND SPHINCTER OF ODDI
- Novel prodrugs of meropenem with two lipophilic promoieties : synthesis and pharmacokinetics
- Effect of alismol on adrenergic mechanism in isolated rabbit ear artery.
- Nitroglycerin-sensitive and -resistant contractions mediated by receptor-operated calcium channels in rabbit ear artery.
- Water-immersion stress induces mucosal ischemia due to thromboxane A2-like substance and ulcer formation in rats.
- Involvement of uptake2 mechanism in inactivation of noradrenaline released by tyramine under anoxic conditions in perfused rat heart.
- Contractile response due to endothelium derived contracting factors in dog cerebral artery by cerebrospinal fluid obtained from patients with subarachnoid hemorrhage.
- Inhibitory effects of trimetazidine dihydrochloride on aggregation, serotonin release and malondialdehyde production in rabbit platelets.
- Effect of Indapamide on the Proliferation of Balb/C 3T3 Cells Induced by Platelet-Derived Growth Factor.