Casagrande C, Merlo L, Ferrini R, Miragoli G, Semeraro C
Simes Cardiovascular Research Centre, Zambon Group, Cormano, Milan, Italy.
J Cardiovasc Pharmacol. 1989;14 Suppl 8:S40-59.
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.
将多巴胺转化为口服活性前药可增强利用其心血管和肾脏作用进行治疗的可能性。在概述这些前药开发的药物化学基础之后,对异波帕明、左旋多巴、谷多巴和TA - 870的实验室和临床药理学进行了综述,一方面指出了在心力衰竭、原发性高血压和肾衰竭方面各种初步研究的有趣指征,另一方面指出了异波帕明作为“血管扩张性正性肌力药”在慢性充血性心力衰竭治疗中的广泛治疗经验。还报告了异波帕明和新型前药Sim 2055(即表肾上腺素 - 4 - O - 磷酸酯)的新实验结果。后者在犬口服给药时表现为选择性肾血管扩张剂,因此建议在肾衰竭和原发性高血压中进行临床研究。