Comparison of Cardiorenal and Emetic Effects of Dopamine Prodrugs Docarpamine (TA-870) and Levodopa in Dogs

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Positive inotropic and renal vasodilatory effects of a novel dopamine prodrug, docarpamine, [N-(N-acetyl-L-methionyl)-3,4-bis (ethoxycarbonyl) dopamine ; TA-870] and those of levodopa were compared in anesthetized dogs, and emetic effects of the two drugs were compared in conscious dogs. Intraduodenal administrations of docarpamine and levodopa at 20 mg/kg produced similar increases in cardiac contractility. The maximal increases in the left ventricular dP/dt_<max> after docarpamine and levodopa were 36.6±14.2 and 39.2±12.1%, respectively. The two drugs also produced similar decreases in renal vascular resistance (21.2±2.2 and 13.6±3.4%, respectively) and increases in renal blood flow (27.9±3.2 and 17.9±5.2%, respectively), however, the duration of renal vasodilation after docarpamine was longer than that of levodopa. Oral administration of the two drugs in conscious dogs produced vomiting. The ED_<50> value of the emetic effect for docarpamine was greater than 160 mg/kg, and that for levodopa was 11.0 mg/kg. The emesis was inhibited by pretreatment with a DA_2 antagonist, domperidone. In conclusion, docarpamine and levodopa produced similar cardiorenal effects, but the emetic effect of docarpamine was much weaker than that of levodopa. Docarpamine can be used as a selective dopamine prodrug for the peripheral circulation.
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