Reversal of Multidrug Resistance by New Dihydropyridines with Low Calcium Antagonist Activity

Authors

  • Laura Capolongo Pharmacìa-Farmitalia Carlo Erba., Research Center R.&D./Business Area Oncology — Oncology Lab., Nerviano, Italy
  • Nadia Amboldi Pharmacìa-Farmitalia Carlo Erba., Research Center R.&D./Business Area Oncology — Oncology Lab., Nerviano, Italy
  • Dario Ballinari Pharmacìa-Farmitalia Carlo Erba., Research Center R.&D./Business Area Oncology — Oncology Lab., Nerviano, Italy
  • Paolo Cozzi Pharmacìa-Farmitalia Carlo Erba., Research Center R.&D./Business Area Oncology — Oncology Lab., Nerviano, Italy
  • Giulia Melegaro Pharmacìa-Farmitalia Carlo Erba., Research Center R.&D./Business Area Oncology — Oncology Lab., Nerviano, Italy
  • Marina Ripamonti Pharmacìa-Farmitalia Carlo Erba., Research Center R.&D./Business Area Oncology — Oncology Lab., Nerviano, Italy
  • Fabrizio Vaghi Pharmacìa-Farmitalia Carlo Erba., Research Center R.&D./Business Area Oncology — Oncology Lab., Nerviano, Italy
  • Maria Grandi Pharmacìa-Farmitalia Carlo Erba., Research Center R.&D./Business Area Oncology — Oncology Lab., Nerviano, Italy

DOI:

https://doi.org/10.3109/02841869409083949

Abstract

The clinical use of Ca++ antagonist agents as modulators of multidrug resistance is limited by their strong vasodilator activity. This study reports data obtained by testing a series of new 1,4 dihydropyridine derivatives (DHPs) for their in vitro resistance modulating activity and their Ca++ antagonist effect. All the tested DHPs are active to increase doxorubicin activity with dose modifying factor values ranging between 2 and 47 on P388/DX cells and 12 and 36 on LoVo/DX cells. Their resistance modulating action is exerted through an increase of DX intracellular level. The Ca++ antagonist activity of DHPs, evaluated as capacity to inhibit the KCl-induced contractions in isolated Guinea pig ileum strips, is not related to their resistance modulating activity. This finding makes it possible to select, for further in vivo evaluations, compounds IX, X and XI, which have strong ability to overcome multidrug resistance and low Ca++ antagonist effect.

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Published

1994-01-01

How to Cite

Capolongo, L. ., Amboldi, N. ., Ballinari, D. ., Cozzi, P. ., Melegaro, G. ., Ripamonti, M. ., … Grandi, M. . (1994). Reversal of Multidrug Resistance by New Dihydropyridines with Low Calcium Antagonist Activity. Acta Oncologica, 33(7), 787–791. https://doi.org/10.3109/02841869409083949

Issue

Vol. 33 No. 7 (1994): Acta Oncologica

Section

Articles