Effects of a 2-substituted adenosine derivative, 2-(p-methoxyphenyl)-adenosine (CV-1674) on coronary and cardiohemodynamics, and myocardial energetics.

In dogs, intracoronary doses of CV-1674, adenosine ( ADS) and 2-Cl-ADS for doubling coronary flow were estimated as 5.0, 2.0 and 0.4 microgram/dog, and i.v. doses 31, 71 and 2.5 microgram/kg, respectively. ADS and 2-Cl-ADS decreased, while CV-1674 increased LV dp/dt. Intravenous infusion (30 min) of CV-1674 (10 microgram/kg per min) and ADS (700 microgram/kg per min) decreased coronary resistance to approximately the same extent. Decreases in blood pressure, total peripheral resistance and myocardial O2 concumption with ADS were more prominent than those with CV-1674. ADS produced a marked bradycardia that was not evident with CV-1674. Neither agent had a significant influence on myocardial efficiency. In guinea pig atria, ADS and 2-Cl-ADS exerted negative effects while those with CV-1674 were positive inotropic and chronotropic. In cats, intraduodenal ADS (10 mg/kg) produced no effects on cardiohemodynamic parameters. CV-1674 (250 and 500 microgram/kg) increased myocardial tissue blood flow (MBF) with a slight hypotension in a dose-dependent manner, whereas 2-Cl-ADS (100, 250 and 500 microgram/kg) increased MBF only with the highest dose concomitantly with marked hypotension and bradycardia. These results suggest that CV-1674 induces selective coronary vasodilation with less depression on cardiohemodynamics, and is relatively well absorbed from the intestinal tract. The pharmacological profile of the compound, therefore, differs from that of ADS and 2-Cl-ADS.