title: Effects of R-enantiomer (GR66234A) and L-enantiomer (GR66235A) of telupidine, a new dihydropyridine derivative, on cell lines displaying the multidrug resistant phenotype.
abstract: BACKGROUND
  Many dihydropyridine analogues with calcium channel blocker activity are able to reverse multidrug resistance (MDR). We studied the daunorubicin resistance reversing activity of the R enantiomer (GR66234A) and the L-enantiomer (GR66235 A) of teludipine, a new lipophilic calcium channel blocker synthesized by Glaxo.
  
  
  METHODS
  The daunorubicin resistance reversing activity of the enantiomers of teludipine was evaluated in two MDR cell lines: ARNII, an erythroleukemia cell line which expresses p-glycoprotein, and MCF 7/R, a breast cancer cell line with p-glycoprotein and high levels of glutathione S transferase (GST) and glutathione peroxidase (GSH Px).
  
  
  RESULTS
  GR66234A and GR66235A show the same activity in reversing daunorubicin resistance and are more effective than verapamil. The difference in activity between verapamil and the enantiomers of teludipine is greater in ARNII cells than in MCF 7/R cells. Nevertheless, there are no significative differences in cellular daunorubicin accumulation between ARNII and MCF 7/R following exposure to teludipine, nor are there differences in intracellular daunorubicin distribution in the presence of either MDR reversing agent.
  
  
  CONCLUSIONS
  The low calcium channel antagonistic activity of GR66234A suggests that this compound may be useful in combination with chemotherapy in MDR malignancies.
authors: Interdepartimental Center of Research in Clinical Oncology, University of Palermo, Italy.
authors: M
authors: M
authors: Tolomeo
authors: R A
authors: RA
authors: Gancitano
authors: M
authors: M
authors: Musso
authors: F
authors: F
authors: Porretto
authors: R
authors: R
authors: Perricone
authors: V
authors: V
authors: Abbadessa
authors: A
authors: A
authors: Cajozzo
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics; D006801:Humans; D051379:Mice; D010641:Phenotype; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C091233:teludipine; D003630:Daunorubicin