3,5-Dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7): A new multidrug resistance inhibitor devoid of effects on Langendorff-perfused rat heart

Simona Saponara, Antonella Ferrara, Beatrice Gorelli, Anamik Shah, Masami Kawase, Noboru Motohashi, Joseph Molnar, Giampietro Sgaragli, Fabio Fusi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Cardiac effects of 3,5-dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7), a novel multidrug resistance (MDR) inhibitor, in Langendorff-perfused rat heart have been investigated and compared to that of nifedipine. Nifedipine decreased concentration-dependently (IC50 = 8.89 ± 1.09 × 10- 8 M) left ventricular pressure leaving unaltered coronary perfusion pressure, whereas DP7 did not affect both parameters. Nifedipine did not modify both QRS and QT intervals of electrocardiogram (ECG). Second-degree atrioventricular block or ventricular rhythm occurred in presence of nifedipine, however, in 4 out of 6 hearts. DP7, up to 30 μM, failed to alter ECG parameters. In conclusion, DP7, may represent a lead compound for the development of potent dihydropyridine MDR chemosensitizers devoid of cardiac effects.

Original languageEnglish
Pages (from-to)160-163
Number of pages4
JournalEuropean Journal of Pharmacology
Volume563
Issue number1-3
DOIs
Publication statusPublished - Jun 1 2007

Keywords

  • Dihydropyridines
  • Electrocardiogram
  • Langendorff-perfused rat heart

ASJC Scopus subject areas

  • Pharmacology

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