THE CARDIOVASCULAR PHARMACOLOGY OF 7‐PROPYL‐THEOPHYLLINE‐DOPAMINE (D4975); COMPARISON WITH DOPAMINE AND DOBUTAMINE

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Abstract
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 μg/kg) it increased systemic arterial pressure, left ventricular (LV) dP/dtmax, dP/dt at fixed ventricular isovolumic pressures and cardiac output. Heart rate effects were minimal. D4975 was about 5 times more active than dopamine or dobutamine in elevating LV dP/dtmax 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. The effects of D4975 on LV dP/dtmax were greatly reduced by the prior administration of propranolol. D4975 has no effect on peripheral β2‐adrenoceptors. It is suggested that the effects of D4975 on the myocardium involve both β1‐adrenoceptor stimulation and inhibition of phosphodiesterase and that the marked and prolonged pressor response is due to resistance to enzymatic breakdown by monoamine oxidase. 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/dtmax without increasing either heart rate or systemic arterial pressure.