Effects of hexobendine on adenosine metabolism and myocardial energy metabolism

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  • IWATA Heitaroh
    Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University
  • MASUKAWA Tohru
    Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University
  • KAKUNO Katsuhiko
    Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University
  • YAMAMOTO Itaru
    岡山大学薬学部生物薬品製造学教室

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Other Title
  • ヘキソベンジンのアデノシン代謝ならびに心筋代謝に対する影響
  • Hexobendine ノ Adenosine タイシャ ナラビニ シンキン

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Description

To elucidate the mode of action of hexobendine, its effects cn some enzyme activities, the uptake of adenosine by rat erythrocytes and changes in the concentration of various myocardial substrates following induced hypoxia in rat were studied. Hexobendine had no effect on the in vitro activities of the adenosine degrading enzyme, adenosine deaminase and of the A-PRTase, HG-PRTase which are associated with the salvage pathways of purine biosyntheses. The uptake of adenosine by rat erythrccytes in vitro was inhibited considerably by hexobendine. Hypoxic states resulted in a significant decrease in creatine phosphate, ATP, glycogen and glucose contents, and increase in ADP, AMP, adenosine and lactate contents in rat myocardials. These alterations in cardiac metabolism induced by hypoxia were significantly improved by hexobendine given orally in doses of 10 ?? 100 mg/kg. Thus, hexobendine was shown to maintain the normal aerobic energy metabolism of the heart under states of hypoxia. In such states adenosine may be released from tissues and this increase in the available concentration of adenosine in plasma through inhibition of uptake by erythrocytes may be involved in the coronary vasodilating action of hexobendine.

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