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Chemical Compound Review

Noverapamil     2-(3,4-dimethoxyphenyl)-5-[2- (3,4...

Synonyms: Norverapamil, CHEMBL1298, AGN-PC-00PTGG, SureCN222066, CHEBI:355870, ...
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Disease relevance of Noverapamil


High impact information on Noverapamil

  • The concentrations of verapamil and norverapamil, as well as their enantiomers, were quantified in serum by chiral HPLC [6].
  • Values for the maximum rate of metabolism (V(max)) of verapamil N-dealkylation (formation of D-617) and N-demethylation (formation of norverapamil) activities correlated with the CYP3A4 protein content in both organs [7].
  • Concentrations of talinolol, verapamil, and its main metabolite norverapamil were measured in serum with HPLC [8].
  • Norverapamil AUC also rose from 1225 +/- 405 to 2312 +/- 963 ng/ml/hr during the attainment of steady state [1].
  • Additionally, norverapamil and reserpine have, respectively, a 60- and 40-fold preference for inhibition of P-gp over CYP3A4 [9].

Biological context of Noverapamil


Anatomical context of Noverapamil


Associations of Noverapamil with other chemical compounds


Gene context of Noverapamil

  • At 50 microM, norverapamil showed time-dependent inhibition of CYP3A5 (30%), but to a much lesser extent compared with that of CYP3A4 (80%) [16].
  • Specific antibodies directed against CYP3A were used to inhibit formation of D-617 and norverapamil [24].
  • Vincristine binding to solutions of alpha 1-acid glycoprotein (AGP, 2 mg/ml) and the effect of D,L-verapamil, verapamil enantiomers and the verapamil metabolites norverapamil and D617 were investigated in vitro using equilibrium dialysis and 3H-labelled vincristine [25].
  • Interestingly, P450 2C8 readily metabolized both S- and R-verapamil to D-617, norverapamil and PR-22 with only slightly higher Km values than noted for P450s 3A4 and 3A5 [26].
  • In contrast, P450 2C8 produced both the D-620 and PR-22 metabolites from the enantiomers of norverapamil, again with stereoselective preference seen for the S-enantiomer [26].

Analytical, diagnostic and therapeutic context of Noverapamil


  1. Reduced verapamil clearance during long-term oral administration. Shand, D.G., Hammill, S.C., Aanonsen, L., Pritchett, E.L. Clin. Pharmacol. Ther. (1981) [Pubmed]
  2. Continuous-infusion verapamil with etoposide in relapsed or resistant paediatric cancers. Cowie, F.J., Pinkerton, C.R., Phillips, M., Dick, G., Judson, I., McCarthy, P.T., Flanagan, R.J. Br. J. Cancer (1995) [Pubmed]
  3. The pharmacokinetics of racemic verapamil in patients with impaired renal function. Zachariah, P.K., Moyer, T.P., Theobald, H.M., Frantz, R.P., Kurtz, S.B., McCarthy, J.T., Smith, R.L. Journal of clinical pharmacology. (1991) [Pubmed]
  4. Verapamil and norverapamil plasma levels in infants and children during chronic oral treatment. Piovan, D., Padrini, R., Svalato Moreolo, G., Magnolfi, G., Milanesi, O., Zordan, R., Pellegrino, P.A., Ferrari, M. Therapeutic drug monitoring. (1995) [Pubmed]
  5. Effects of the pre-column in automated on-column injection capillary gas chromatography. Arrendale, R.F., Stewart, J.T., Martin, R.M. J. Chromatogr. (1990) [Pubmed]
  6. The effect of short- and long-term administration of verapamil on the disposition of cytochrome P450 3A and P-glycoprotein substrates. Lemma, G.L., Wang, Z., Hamman, M.A., Zaheer, N.A., Gorski, J.C., Hall, S.D. Clin. Pharmacol. Ther. (2006) [Pubmed]
  7. Cytochrome P450 3A4 and P-glycoprotein expression in human small intestinal enterocytes and hepatocytes: a comparative analysis in paired tissue specimens. von Richter, O., Burk, O., Fromm, M.F., Thon, K.P., Eichelbaum, M., Kivistö, K.T. Clin. Pharmacol. Ther. (2004) [Pubmed]
  8. Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans. Schwarz, U.I., Gramatté, T., Krappweis, J., Berndt, A., Oertel, R., von Richter, O., Kirch, W. Clin. Pharmacol. Ther. (1999) [Pubmed]
  9. Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Wang, E., Lew, K., Barecki, M., Casciano, C.N., Clement, R.P., Johnson, W.W. Chem. Res. Toxicol. (2001) [Pubmed]
  10. Differences in oral verapamil absorption as a function of time of day. Eldon, M.A., Battle, M.M., Voigtman, R.E., Colburn, W.A. Journal of clinical pharmacology. (1989) [Pubmed]
  11. Enantioselective kinetics of verapamil and norverapamil in isolated perfused rat livers. Mehvar, R., Reynolds, J.M., Robinson, M.A., Longstreth, J.A. Pharm. Res. (1994) [Pubmed]
  12. Influence of metabolites on protein binding of verapamil enantiomers. Johnson, J.A., Akers, W.S. British journal of clinical pharmacology. (1995) [Pubmed]
  13. Postabsorption concentration peaks with brand-name and generic verapamil: a double-blind, crossover study in elderly hypertensive patients. Saseen, J.J., Porter, J.A., Barnette, D.J., Bauman, J.L., Zajac, E.J., Carter, B.L. Journal of clinical pharmacology. (1997) [Pubmed]
  14. Once a day verapamil in essential hypertension. Müller, F.B., Ha, H.R., Hotz, H., Schmidlin, O., Follath, F., Bühler, F.R. British journal of clinical pharmacology. (1986) [Pubmed]
  15. Rapid high-performance liquid chromatographic method for the measurement of verapamil and norverapamil in blood plasma or serum. Cole, S.C., Flanagan, R.J., Johnston, A., Holt, D.W. J. Chromatogr. (1981) [Pubmed]
  16. Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Wang, Y.H., Jones, D.R., Hall, S.D. Drug Metab. Dispos. (2005) [Pubmed]
  17. Verapamil and norverapamil in plasma and breast milk during breast feeding. Anderson, P., Bondesson, U., Mattiasson, I., Johansson, B.W. Eur. J. Clin. Pharmacol. (1987) [Pubmed]
  18. Effects of verapamil enantiomers and major metabolites on the cytotoxicity of vincristine and daunomycin in human lymphoma cell lines. Häussermann, K., Benz, B., Gekeler, V., Schumacher, K., Eichelbaum, M. Eur. J. Clin. Pharmacol. (1991) [Pubmed]
  19. Verapamil metabolites: potential P-glycoprotein-mediated multidrug resistance reversal agents. Woodland, C., Koren, G., Wainer, I.W., Batist, G., Ito, S. Can. J. Physiol. Pharmacol. (2003) [Pubmed]
  20. Direct determination of the enantiomeric ratio of verapamil, its major metabolite norverapamil and gallopamil in plasma by chiral high-performance liquid chromatography. Fieger, H., Blaschke, G. J. Chromatogr. (1992) [Pubmed]
  21. Evaluation of potential pharmacodynamic and pharmacokinetic interactions between verapamil and propranolol in normal subjects. Murdoch, D.L., Thomson, G.D., Thompson, G.G., Murray, G.D., Brodie, M.J., McInnes, G.T. British journal of clinical pharmacology. (1991) [Pubmed]
  22. Increased intracellular concentrations of doxorubicin in resistant lymphoma cells in vivo by concomitant therapy with verapamil and cyclosporin A. Tidefelt, U., Juliusson, G., Elmhorn-Rosenborg, A., Peterson, C., Paul, C. Eur. J. Haematol. (1994) [Pubmed]
  23. Effect of naringin pretreatment on bioavailability of verapamil in rabbits. Yeum, C.H., Choi, J.S. Arch. Pharm. Res. (2006) [Pubmed]
  24. Identification of P450 enzymes involved in metabolism of verapamil in humans. Kroemer, H.K., Gautier, J.C., Beaune, P., Henderson, C., Wolf, C.R., Eichelbaum, M. Naunyn Schmiedebergs Arch. Pharmacol. (1993) [Pubmed]
  25. Effect of D,L-verapamil, verapamil enantiomers and verapamil metabolites on the binding of vincristine to alpha 1-acid glycoprotein. Woodcock, B.G., Abdel-Rahman, M.S., Wosch, F., Harder, S. Eur. J. Cancer (1993) [Pubmed]
  26. Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamil. Tracy, T.S., Korzekwa, K.R., Gonzalez, F.J., Wainer, I.W. British journal of clinical pharmacology. (1999) [Pubmed]
  27. An evaluation of the pharmacokinetics, pharmacodynamics, and dialyzability of verapamil in chronic hemodialysis patients. Hanyok, J.J., Chow, M.S., Kluger, J., Izard, M.W. Journal of clinical pharmacology. (1988) [Pubmed]
  28. Simultaneous quantitation of verapamil, norverapamil, and N-dealkylated metabolites in human plasma following oral administration. Kapur, P.A., Law, T., Watson, E. J. Chromatogr. (1985) [Pubmed]
  29. Verapamil and norverapamil determination in human plasma by gas-liquid chromatography using nitrogen-phosphorus detection: application to single-dose pharmacokinetic studies. Abernethy, D.R., Todd, E.L., Mitchell, J.R. Pharmacology (1984) [Pubmed]
  30. Stereoselective determination of verapamil and norverapamil by capillary electrophoresis. Dethy, J.M., De Broux, S., Lesne, M., Longstreth, J., Gilbert, P. J. Chromatogr. B, Biomed. Appl. (1994) [Pubmed]
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