Abstract |
The effects of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a] pyridine, CAS 94457-09-7) on infarct size, myeloperoxidase (MPO) activity and plasma prostanoid levels were studied using coronary artery occlusion (1 h)-reperfusion (3 h) model in rabbits, comparing with acetylsalicylic acid (ASA). Myocardial infarct size, MPO activity in the infarcted region and plasma glutamate oxalo- acetate transaminase, lactate dehydrogenase and creatine kinase were significantly suppressed by treatment with KC-764 (2 mg/kg i.v.), but not by ASA (10 mg/kg i.v.). KC-764 completely depressed the increase in plasma TXB2 level during occlusion-reperfusion with a little influence on plasma 6-keto-PGF1 alpha. Thus, the ratio of 6-keto-PGF1 alpha to TXB2 levels was increased by KC-764. On the other hand, ASA treatment depressed both plasma TXB2 and 6-keto-PGF1 alpha levels to the same extent. The in vitro study with guinea-pig neutrophils showed that KC-764 reduced the chemotaxis induced by formyl- methionyl-leucyl- phenylalanine at 3 x 10(7)-3 x 10(-6) mol/l, while ASA did not influence the neutrophil chemotaxis. These results suggest that KC-764 may salvage the damaged ischemic myocardium by the selective inhibition of TXA2 synthesis and the suppression of leukocyte migration.
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Authors | S Ohmuro, Y Tsukada, F Taga, H Ohkubo, H Uchida |
Journal | Arzneimittel-Forschung
(Arzneimittelforschung)
Vol. 42
Issue 1
Pg. 39-42
(Jan 1992)
ISSN: 0004-4172 [Print] Germany |
PMID | 1586378
(Publication Type: Journal Article)
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Chemical References |
- Bridged Bicyclo Compounds
- Nicotinic Acids
- Platelet Aggregation Inhibitors
- Thromboxane B2
- 6-Ketoprostaglandin F1 alpha
- N-Formylmethionine Leucyl-Phenylalanine
- KC 764
- L-Lactate Dehydrogenase
- Aspartate Aminotransferases
- Creatine Kinase
- Aspirin
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Topics |
- 6-Ketoprostaglandin F1 alpha
(pharmacology)
- Animals
- Aspartate Aminotransferases
(blood)
- Aspirin
(pharmacology)
- Bridged Bicyclo Compounds
(pharmacology)
- Chemotaxis, Leukocyte
(drug effects)
- Creatine Kinase
(blood)
- Guinea Pigs
- L-Lactate Dehydrogenase
(blood)
- Male
- Myocardial Infarction
(physiopathology, prevention & control)
- Myocardial Reperfusion Injury
(prevention & control)
- N-Formylmethionine Leucyl-Phenylalanine
(pharmacology)
- Neutrophils
(drug effects)
- Nicotinic Acids
(pharmacology)
- Platelet Aggregation Inhibitors
(therapeutic use)
- Rabbits
- Thromboxane B2
(blood)
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