Effects of MCI-176, a new quinazolinone calcium antagonist, on myocardial energy and carbohydrate metabolism in ischemic dog hearts.
The effect of 2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)- 6-isopropoxy-4(3H)-quinazolinone hydrochloride (MCI-176), a calcium antagonist, on ischemic myocardial metabolism was studied in dog hearts subjected to an occlusion of the left anterior descending coronary artery (LAD) for 3 or 30 min. MCI-176 (0.03 or 0.1 mg/kg), when injected i.v. 5 min before occlusion, increased coronary blood flow and decreased systemic aortic pressure. When the LAD was ligated, the levels of creatine phosphate, ATP, total adenine nucleotides and energy change potential decreased in the ischemic myocardium. Three minutes after ischemia, MCI-176 (0.1 mg/kg) significantly (P less than 0.05) diminished these impairments of energy metabolism. Even 30 min after ischemia, pretreatment with MCI-176 tended to lessen the depletion of ATP and total adenine nucleotides, although these effects were not statistically significant. Myocardial ischemia produced a breakdown of glycogen, an accumulation of lactate, and an inhibition of glycolytic flux through phosphofructokinase reaction. MCI-176 (0.1 mg/kg) significantly (P less than 0.05) reduced these alterations of carbohydrate metabolism after 3 min of ischemia. These results suggest that pretreatment with MCI-176 reduces the impairments of myocardial energy and carbohydrate metabolism in ischemic dog hearts, suggesting that the drug is capable of improving the imbalance between oxygen supply and oxygen demand in the ischemic myocardium.
Abe
Y
Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Ichihara
K
K
Abiko
Y
Y
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D003327:Coronary Disease / Q000378:metabolism* / Q000517:prevention & control; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D010732:Phosphofructokinase-1 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D052999:Quinazolinones
D000227:Adenine Nucleotides; D002121:Calcium Channel Blockers; D011799:Quinazolines; D052999:Quinazolinones; D010725:Phosphocreatine; C050606:MCI 176; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1