The Cardiovascular Pharmacology of 7‐propyl‐theophylline‐dopamine (D4975); Comparison With Dopamine and Dobutamine

Abstract

I The effects of a newly developed dopamine-xanthine derivative, 7-propyl-theophylline-dopamine (D4975), have been examined in cats anaesthetized with sodium pentobarbitone. When administered intravenously (in doses as low as 0.5 to 1.0 tg/kg) it increased systemic arterial pressure, left ventricular (LV) dP/dt,,,x, dP/dt at fixed ventricular isovolumic pressures and cardiac output. Heart rate effects were minimal.2 D4975 was about 5 times more active than dopamine or dobutamine in elevating LV dP/dt,... or dP/dt at common peak isovolumic pressures (CPIP) and about 10 times more active than dopamine at increasing systemic arterial blood pressure. The effects of D4975 were also more prolonged than those of the other two agents.3 The effects of D4975 on LV dP/dt,,,,, were greatly reduced by the prior administration of propranolol. D4975 has no effect on peripheral fJ2-adrenoceptors.4 It is suggested that the effects of D4975 on the myocardium involve both fl1-adrenoceptor stimulation and inhibition of phosphodiesterase and that the marked and prolonged pressor response is due to resistance to enzymatic breakdown by monoamine oxidase.5 The results suggest that D4975 might prove valuable in the treatment of the hypotension and reduced myocardial contractility of shock, especially as it is possible to select a dose that increases LV dP/dt,,.l without increasing either heart rate or systemic arterial pressure.

Noninvasive monitoring of hemodynamic stress using quantitative near-infrared frequency-domain photon migration spectroscopy

“…Dobutamine increases cardiac output and elevates pulmonary artery pressure. 45,46 Our results show that dobutamine increased CO and mPAP in a dose-dependent manner ͑Figure 7͒. Analysis of the dobutamine data indicates that FDPM-derived ͓TotHb͔ and S t O 2 are statistically correlated with dobutaminemediated changes in CO.…”

Effects of increasing infusion rates of dopamine, dobutamine, epinephrine, and phenylephrine in healthy anesthetized cats

“…In the study reported here, there was a 17-fold difference between concentrations measured in 2 cats during an infusion rate of 5 μg/kg/min. Dobutamine has been used in a number of studies, [15][16][17] and in 2 studies, 18,19 dobutamine was used in cats anesthetized with inhalants. In cats anesthetized with pentobarbital, dobutamine increased contractility without increasing heart rate or blood pressure.…”

Agents for the treatment of heart failure

“…In humans, elimination of amrinone follows first-order kinetics with a half-life of 2.6 h.123 The synthesis of amrinone labeled with 14C at C-3 has been reported. lz4 Win 47203 has been described as an analog of amrinone which is 10-30 times more potent than amrinone, with a therapeutic index of 100 [4,5-blpyridines, AR-L57 CL and AR-LlOo BS, were also studied. AR-L57 CL is inactive orally, presumably due t o its low solubility a t physiological pH.lZ7 Likewise, AR-Lroo BS was not active orally, which was attributed t o rapid metabolism and a slow absorption rate.…”