To elucidate the mode of action of
hexobendine, its effects on 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 erythrocytes in vitro was inhibited considerably by
hexobendine. Hypoxic states results 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 approximately 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.