Cardiovascular and renal action of dopaminergic prodrugs.
The possibility of exploiting the cardiovascular and renal action of dopamine for therapeutic purposes is enhanced by its conversion into orally active prodrugs. Following an outline of the medicinal chemistry bases of the development of these prodrugs, laboratory and clinical pharmacology of ibopamine, levodopa, gludopa, and TA-870 are reviewed, pointing out the interesting indications of various preliminary studies in heart failure, essential hypertension, and renal failure on the one hand, and the extensive therapeutic experience with ibopamine as an "inodilator" in the chronic treatment of congestive heart failure on the other hand. New experimental results are also reported for ibopamine and for the novel prodrug Sim 2055, i.e., epinine-4-O-phosphate. The latter is shown to act as a selective renal vasodilator on oral administration in dogs and it is therefore proposed for clinical investigation in renal failure and in essential hypertension.
Casagrande
C
C
Simes Cardiovascular Research Centre, Zambon Group, Cormano, Milan, Italy.
Merlo
L
L
Ferrini
R
R
Miragoli
G
G
Semeraro
C
C
D000818:Animals; D002316:Cardiotonic Agents; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D003846:Deoxyepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D014665:Vasodilator Agents
D002316:Cardiotonic Agents; D015259:Dopamine Agents; D011355:Prodrugs; D014665:Vasodilator Agents; D007980:Levodopa; C017342:gamma-glutamyl DOPA; D004295:Dihydroxyphenylalanine; C023487:ibopamine; D003846:Deoxyepinephrine; C052143:docarpamine; D004298:Dopamine