Attempts to improve the selectivity of calcium antagonistic drugs

The dihydropyridine calcium antagonists differ in respect to their structures as well as their pharmacological profiles. An improved vascular selectivity has been claimed for some of the newer agents (amlodipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine and nicardipine), implying that these agents exert a stronger action on the resistance and coronary arteries than on myocardial and nodal structures. By virtue of their antihypertensive effects, calcium antagonists should be considered as renal protective. Such a renal protective potential has been demonstrated in renal insufficiency and toxicity caused by cancer chemotherapy, radiocontrast agents, cyclosporine or aminoglycoside antibiotics. Furthermore, calcium antagonists may also have a protective effect on donor kidneys in kidney transplantation. Among the newer dihydropyridines, manidipine has been suggested as possessing a certain degree of renal selectivity. This claim is based mainly on animal experimental studies and has to be substantiated in the clinic. From the therapeutic point of view, the concept of renal selectivity for calcium antagonists may be of considerable interest.