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Identification of a new cardioprotective agent—6(2‐isopropylaminopropyl)‐3‐pyridinol
Author(s) -
Schaffer Stephen W.,
Tan Boen H.,
Lampson William G.,
Oei Howard H. H.,
Glenn Thomas M.
Publication year - 1985
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430050406
Subject(s) - hypoxanthine , ischemia , chemistry , xanthine oxidase , glycolysis , pharmacology , adenosine triphosphate , oxygen , reactive oxygen species , biochemistry , inotrope , medicine , metabolism , enzyme , organic chemistry
Abstract The effect of 6(2‐isopropylaminopropyl)‐3‐pyridinol fumarate (CGS 5649B) on mechanical function and tissue energy levels of the isolated rat heart subjected to 35 min of global ischemia and 25 min of reperfusion was examined. Hearts perfused with buffer supplemented with the drug (0.03–0.4 mM) showed an improvement in the recovery of mechanical function and an attenuation in the loss of tissue adenosine triphosphate (ATP) levels following the 25‐min reperfusion period. In nonischemic tissue, the drug mediated a positive inotropic effect, a slight increase in glucose utilization and oxygen consumption, and a significant change in the levels of some key glycolytic intermediates. It also quenched hydroxyl radicals produced by a hypoxanthine‐xanthine oxidase reaction system. These results suggest that CGS 5649B has a beneficial effect on hearts subjected to ischemia by reducing energy demand. This may be related to its ability to scavenge highly reactive oxygen species.