Development of dopaminergic drugs for the chronic treatment of congestive heart failure.
1. The search of orally active dopaminergic drugs for the chronic treatment of congestive heart failure has followed two different approaches. 2. On the one hand, a selective DA-1 receptor agonist, such as fenoldopam, has been investigated as an agent developed for the stimulation of vascular and tubular DA-1 receptors in the kidney. On the other hand, orally active prodrugs were synthetized with the aim of mimicking the full pattern of dopaminergic and adrenergic actions of intravenous dopamine. 3. Ibopamine, the diisobutyric ester of N-methyldopamine, has shown effects comparable to those of dopamine in various animal models and in clinical investigations. Furthermore, patients suffering from mild or severe congestive heart failure were shown to benefit from ibopamine treatment in a number of therapeutic trials. 4. Limited experience is currently available on other prodrugs, such as docarpamine and Sim 2055, i.e. the 4-0-phosphate ester of N-methyldopamine. The latter is an analogue of ibopamine designed for a preferential delivery of N-methyldopamine in the kidney. 5. Based upon some additional studies with levodopa, the results suggest that a combination of DA-1 and DA-2 agonistic activity is a desirable feature of a new drug, since it appears suitable to provide vasodilation while counteracting the neurohumoral abnormality of congestive heart failure.
Casagrande
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C
Simes Cardiovascular Research Centre, Cormano, Milan, Italy.
Merlo
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L
La Regina
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A
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D003846:Deoxyepinephrine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004298:Dopamine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015259:Dopamine Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018818:Fenoldopam; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C023487:ibopamine; D018818:Fenoldopam; D003846:Deoxyepinephrine; C052143:docarpamine; D004298:Dopamine