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Chemical Compound Review

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

Synonyms: Falicard, Finoptin, Isoptine, Isoptin, Izoptin, ...
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Disease relevance of VERAPAMIL


Psychiatry related information on VERAPAMIL


High impact information on VERAPAMIL


Chemical compound and disease context of VERAPAMIL


Biological context of VERAPAMIL


Anatomical context of VERAPAMIL

  • The discovery that verapamil partially reverses chloroquine resistance in vitro led to the proposal that efflux may involve an ATP-driven P-glycoprotein pump similar to that in mammalian multidrug-resistant (mdr) tumor cell lines [25].
  • The calcium channel blockers, verapamil and diltiazem, inhibit phytohemagglutinin (PHA)-induced mitogenesis at concentrations that block the T lymphocyte K channel currents [26].
  • IMPLICATIONS: In vitro sensitization by the addition of verapamil in cell lines with these low levels of mdr-1/Pgp suggests that clinically detected levels may confer drug resistance in vivo [27].
  • Hence, our data strongly suggest that pharmacological intervention with verapamil merits investigation as a potential therapeutic option not only for patients with sarcoglycan mutations, but also for patients with idiopathic cardiomyopathy associated with myocardial ischemia not related to atherosclerotic coronary artery disease [28].
  • Using mouse models of cardiomyopathy made by ablating genes for components of the sarcoglycan complex, we show that long-term treatment with verapamil, a calcium channel blocker with vasodilator properties, can alleviate the severe cardiomyopathic phenotype, restoring normal serum levels for cardiac troponin I and normal cardiac muscle morphology [28].

Associations of VERAPAMIL with other chemical compounds


Gene context of VERAPAMIL

  • The inhibitory effect of UIC2 in vitro was as strong as that of verapamil (a widely used Pgp inhibitor) at its highest clinically achievable concentrations [34].
  • A time-dependent flux of IL-2 across dense monolayers, which was partially inhibited by Ver, was observed [35].
  • Release of IL-4 and IFN-gamma was significantly inhibited by Ver, Tmx, and UIC2; however, release of IL-6 remained unaffected [35].
  • E217G neither stimulated MDR1 ATPase activity nor inhibited verapamil-stimulated ATPase activity [36].
  • For the latter two drugs, MRP transfectants, which were approximately 8- and approximately 10-fold more sensitive than control cells in the absence of verapamil, exhibited 3.8- and 3.3-fold relative sensitization with 10 microM verapamil, respectively, but remained approximately 2 and approximately 3-fold more resistant than control cells [37].

Analytical, diagnostic and therapeutic context of VERAPAMIL


  1. Treatment of multifocal atrial tachycardia with verapamil. Levine, J.H., Michael, J.R., Guarnieri, T. N. Engl. J. Med. (1985) [Pubmed]
  2. Verapamil-induced atrial fibrillation. Falk, R.H., Knowlton, A.A., Manaker, S. N. Engl. J. Med. (1988) [Pubmed]
  3. Hypotension after quinidine plus verapamil. Possible additive competition at alpha-adrenergic receptors. Maisel, A.S., Motulsky, H.J., Insel, P.A. N. Engl. J. Med. (1985) [Pubmed]
  4. A controlled trial of verapamil for Prinzmetal's variant angina. Johnson, S.M., Mauritson, D.R., Willerson, J.T., Hillis, L.D. N. Engl. J. Med. (1981) [Pubmed]
  5. Verapamil, syncope, and hypertrophic obstructive cardiomyopathy. Trohman, R.G., Feldman, T., Palomo, A.R., Kessler, K.M., Myerberg, R.J. N. Engl. J. Med. (1986) [Pubmed]
  6. Bizarre perceptual disorder of extremities in patients taking verapamil. Kumana, C.R., Mahon, W.A. Lancet (1981) [Pubmed]
  7. Voltage-sensitive calcium channels in spinal nociceptive processing: blockade of N- and P-type channels inhibits formalin-induced nociception. Malmberg, A.B., Yaksh, T.L. J. Neurosci. (1994) [Pubmed]
  8. Verapamil prophylaxis in pregnant women with bipolar disorder. Goodnick, P.J. The American journal of psychiatry. (1993) [Pubmed]
  9. Controlled study of verapamil for treatment of panic disorder. Klein, E., Uhde, T.W. The American journal of psychiatry. (1988) [Pubmed]
  10. Verapamil vs quinine in recumbent nocturnal leg cramps in the elderly. Farber, H.I. Arch. Intern. Med. (1990) [Pubmed]
  11. Chemical injury of the oral mucosa from verapamil. Guttenberg, S.A. N. Engl. J. Med. (1990) [Pubmed]
  12. Detection of ligand-activated conductive Ca2+ channels in human B lymphocytes. MacDougall, S.L., Grinstein, S., Gelfand, E.W. Cell (1988) [Pubmed]
  13. Reduction of bioavailability of verapamil by rifampin. Rahn, K.H., Mooy, J., Böhm, R., vd Vet, A. N. Engl. J. Med. (1985) [Pubmed]
  14. Verapamil concentrations in cerebrospinal fluid after oral administration. Doran, A.R., Narang, P.K., Meigs, C.Y., Wolkowitz, O.M., Roy, A., Breier, A., Pickar, D. N. Engl. J. Med. (1985) [Pubmed]
  15. Intravenous calcium for fecal impaction secondary to verapamil. Ward, D.J., Ward, J.W., Griffo, W., Rochwarge, A. N. Engl. J. Med. (1982) [Pubmed]
  16. L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. Oudit, G.Y., Sun, H., Trivieri, M.G., Koch, S.E., Dawood, F., Ackerley, C., Yazdanpanah, M., Wilson, G.J., Schwartz, A., Liu, P.P., Backx, P.H. Nat. Med. (2003) [Pubmed]
  17. Reversal of adriamycin resistance by verapamil in human ovarian cancer. Rogan, A.M., Hamilton, T.C., Young, R.C., Klecker, R.W., Ozols, R.F. Science (1984) [Pubmed]
  18. A comparison of verapamil and propranolol for the initial treatment of hypertension. Racial differences in response. Cubeddu, L.X., Aranda, J., Singh, B., Klein, M., Brachfeld, J., Freis, E., Roman, J., Eades, T. JAMA (1986) [Pubmed]
  19. Right ventricular outflow tract tachycardia due to a somatic cell mutation in G protein subunitalphai2. Lerman, B.B., Dong, B., Stein, K.M., Markowitz, S.M., Linden, J., Catanzaro, D.F. J. Clin. Invest. (1998) [Pubmed]
  20. Asystole and cardiogenic shock due to combined treatment with verapamil and flecainide. Buss, J., Lasserre, J.J., Heene, D.L. Lancet (1992) [Pubmed]
  21. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Fidock, D.A., Nomura, T., Talley, A.K., Cooper, R.A., Dzekunov, S.M., Ferdig, M.T., Ursos, L.M., Sidhu, A.B., Naudé, B., Deitsch, K.W., Su, X.Z., Wootton, J.C., Roepe, P.D., Wellems, T.E. Mol. Cell (2000) [Pubmed]
  22. Reversal of multidrug resistance in human colon cancer cells expressing the human MDR1 gene by liposomes in combination with monoclonal antibody or verapamil. Sela, S., Husain, S.R., Pearson, J.W., Longo, D.L., Rahman, A. J. Natl. Cancer Inst. (1995) [Pubmed]
  23. Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver. Reichen, J., Le, M. J. Clin. Invest. (1986) [Pubmed]
  24. L-arginine normalizes endothelial function in cerebral vessels from hypercholesterolemic rabbits. Rossitch, E., Alexander, E., Black, P.M., Cooke, J.P. J. Clin. Invest. (1991) [Pubmed]
  25. Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross. Wellems, T.E., Panton, L.J., Gluzman, I.Y., do Rosario, V.E., Gwadz, R.W., Walker-Jonah, A., Krogstad, D.J. Nature (1990) [Pubmed]
  26. Voltage-gated potassium channels are required for human T lymphocyte activation. Chandy, K.G., DeCoursey, T.E., Cahalan, M.D., McLaughlin, C., Gupta, S. J. Exp. Med. (1984) [Pubmed]
  27. Various methods of analysis of mdr-1/P-glycoprotein in human colon cancer cell lines. Herzog, C.E., Trepel, J.B., Mickley, L.A., Bates, S.E., Fojo, A.T. J. Natl. Cancer Inst. (1992) [Pubmed]
  28. Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex. Cohn, R.D., Durbeej, M., Moore, S.A., Coral-Vazquez, R., Prouty, S., Campbell, K.P. J. Clin. Invest. (2001) [Pubmed]
  29. Purified dihydropyridine-binding site from skeletal muscle t-tubules is a functional calcium channel. Flockerzi, V., Oeken, H.J., Hofmann, F., Pelzer, D., Cavalié, A., Trautwein, W. Nature (1986) [Pubmed]
  30. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. Black, H.R., Elliott, W.J., Grandits, G., Grambsch, P., Lucente, T., White, W.B., Neaton, J.D., Grimm, R.H., Hansson, L., Lacourciere, Y., Muller, J., Sleight, P., Weber, M.A., Williams, G., Wittes, J., Zanchetti, A., Anders, R.J. JAMA (2003) [Pubmed]
  31. Dual Ca2+ requirement for optimal lipid peroxidation of low density lipoprotein by activated human monocytes. Li, Q., Tallant, A., Cathcart, M.K. J. Clin. Invest. (1993) [Pubmed]
  32. Blockage of drug resistance in vitro by disulfiram, a drug used to treat alcoholism. Loo, T.W., Clarke, D.M. J. Natl. Cancer Inst. (2000) [Pubmed]
  33. Expression of mdr1 and mdr3 multidrug-resistance genes in human acute and chronic leukemias and association with stimulation of drug accumulation by cyclosporine. Herweijer, H., Sonneveld, P., Baas, F., Nooter, K. J. Natl. Cancer Inst. (1990) [Pubmed]
  34. Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody. Mechetner, E.B., Roninson, I.B. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  35. Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-gamma in normal human T lymphocytes. Drach, J., Gsur, A., Hamilton, G., Zhao, S., Angerler, J., Fiegl, M., Zojer, N., Raderer, M., Haberl, I., Andreeff, M., Huber, H. Blood (1996) [Pubmed]
  36. Adenosine triphosphate-dependent transport of estradiol-17beta(beta-D-glucuronide) in membrane vesicles by MDR1 expressed in insect cells. Huang, L., Hoffman, T., Vore, M. Hepatology (1998) [Pubmed]
  37. Expression of multidrug resistance-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution. Breuninger, L.M., Paul, S., Gaughan, K., Miki, T., Chan, A., Aaronson, S.A., Kruh, G.D. Cancer Res. (1995) [Pubmed]
  38. The effects of antihypertensive therapy on left ventricular mass in elderly patients. Schulman, S.P., Weiss, J.L., Becker, L.C., Gottlieb, S.O., Woodruff, K.M., Weisfeldt, M.L., Gerstenblith, G. N. Engl. J. Med. (1990) [Pubmed]
  39. Abnormalities in hepatic lipase in chronic renal failure: role of excess parathyroid hormone. Klin, M., Smogorzewski, M., Ni, Z., Zhang, G., Massry, S.G. J. Clin. Invest. (1996) [Pubmed]
  40. Effective treatment of verapamil intoxication with 4-aminopyridine in the cat. Agoston, S., Maestrone, E., van Hezik, E.J., Ket, J.M., Houwertjes, M.C., Uges, D.R. J. Clin. Invest. (1984) [Pubmed]
  41. Systemic toxic effects associated with high-dose verapamil infusion and chemotherapy administration. Pennock, G.D., Dalton, W.S., Roeske, W.R., Appleton, C.P., Mosley, K., Plezia, P., Miller, T.P., Salmon, S.E. J. Natl. Cancer Inst. (1991) [Pubmed]
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