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Protective effect of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine on myocardial damage due to coronary occlusion and reperfusion in rabbit.

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.
AuthorsS Ohmuro, Y Tsukada, F Taga, H Ohkubo, H Uchida
JournalArzneimittel-Forschung (Arzneimittelforschung) Vol. 42 Issue 1 Pg. 39-42 (Jan 1992) ISSN: 0004-4172 [Print] Germany
PMID1586378 (Publication Type: Journal Article)
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
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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