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. 2002 Feb;11(1):53–59. doi: 10.1080/09629350210309

Immunomodulating effects of tofizopam (Grandaxin) and diazepam in vitro.

Sergey V Kalashnikov 1, Elena A Kalashnikova 1, Svetlana N Kokarovtseva 1
PMCID: PMC1781640  PMID: 11926595

Abstract

Benzodiazepines (BDZs) are known to act not only in the central nervous system, but on peripheral cells and tissues binding to the peripheral-type benzodiazepine receptors. In the present study, the influence of two different BDZs (diazepam (Dz) and tofizopam (Tof) on several immune functions has been examined in vitro. Some differences between Dz and Tof in their effects on human lymphocyte proliferative response, changes in glucocorticoid-induced suppression of cell proliferation and influence on cytokine production (tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2)) have been determined. Dz suppressed mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation, enhanced dexamethasone-induced inhibition of PBMC proliferative response, and suppressed lymphocyte production of TNF-alpha and IL-2. Tof usually enhanced PBMC proliferation and IL-2 production in low and moderate doses, but in high doses it suppressed both. Tof in all investigated doses enhanced dexamethasone-induced suppression of lymphocyte proliferation and depressed TNF-alpha production. Thus, both Dz and Tof are shown to have immunomodulating effects in vitro. Tof, opposite to Dz even in the therapeutic doses, is able to enhance in vitro mitogen-induced lymphocyte proliferation and IL-2 production.

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Selected References

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  1. Blalock J. E. The syntax of immune-neuroendocrine communication. Immunol Today. 1994 Nov;15(11):504–511. doi: 10.1016/0167-5699(94)90205-4. [DOI] [PubMed] [Google Scholar]
  2. Cahard D., Canat X., Carayon P., Roque C., Casellas P., Le Fur G. Subcellular localization of peripheral benzodiazepine receptors on human leukocytes. Lab Invest. 1994 Jan;70(1):23–28. [PubMed] [Google Scholar]
  3. Drugan R. C. Are the nonmitochondrial peripheral benzodiazepine receptors on leukocytes a novel intermediary of brain, behavior, and immunity? Lab Invest. 1994 Jan;70(1):1–5. [PubMed] [Google Scholar]
  4. Hopkins S. J., Rothwell N. J. Cytokines and the nervous system. I: Expression and recognition. Trends Neurosci. 1995 Feb;18(2):83–88. [PubMed] [Google Scholar]
  5. Horváth E. J., Salamon C., Bakonyi A., Fekete M. I., Palkovits M. [(3)H]-girisopam, a novel selective benzodiazepine for the 2, 3-benzodiazepine binding site. Brain Res Brain Res Protoc. 1999 Jul;4(2):230–235. doi: 10.1016/s1385-299x(99)00025-2. [DOI] [PubMed] [Google Scholar]
  6. Ikezaki K., Black K. L. Stimulation of cell growth and DNA synthesis by peripheral benzodiazepine. Cancer Lett. 1990 Feb;49(2):115–120. doi: 10.1016/0304-3835(90)90146-o. [DOI] [PubMed] [Google Scholar]
  7. Kelly S., Hertzman C., Daniels M. Searching for the biological pathways between stress and health. Annu Rev Public Health. 1997;18:437–462. doi: 10.1146/annurev.publhealth.18.1.437. [DOI] [PubMed] [Google Scholar]
  8. Kornecki E., Ehrlich Y. H., Lenox R. H. Platelet-activating factor-induced aggregation of human platelets specifically inhibited by triazolobenzodiazepines. Science. 1984 Dec 21;226(4681):1454–1456. doi: 10.1126/science.6150550. [DOI] [PubMed] [Google Scholar]
  9. Lechin F., van der Dijs B., Vitelli-Flores G., Báez S., Lechin M. E., Lechin A. E., Orozco B., Rada I., León G., Jiménez V. Peripheral blood immunological parameters in long-term benzodiazepine users. Clin Neuropharmacol. 1994 Feb;17(1):63–72. doi: 10.1097/00002826-199402000-00007. [DOI] [PubMed] [Google Scholar]
  10. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  11. Mukhin A. G., Zhong P. Y., Krueger K. E. Cofractionation of the 17-kD PK 14105 binding site protein with solubilized peripheral-type benzodiazepine binding sites. Biochem Pharmacol. 1990 Sep 1;40(5):983–989. doi: 10.1016/0006-2952(90)90483-2. [DOI] [PubMed] [Google Scholar]
  12. Olsen R. W., Tobin A. J. Molecular biology of GABAA receptors. FASEB J. 1990 Mar;4(5):1469–1480. doi: 10.1096/fasebj.4.5.2155149. [DOI] [PubMed] [Google Scholar]
  13. Petócz L. A tofizopam (Grandaxin) farmakológiai hatásai. Acta Pharm Hung. 1993 Mar;63(2):79–82. [PubMed] [Google Scholar]
  14. Saano V. Tofizopam selectively increases the action of anticonvulsants. Med Biol. 1986;64(4):201–206. [PubMed] [Google Scholar]
  15. Savino W., Dardenne M. Immune-neuroendocrine interactions. Immunol Today. 1995 Jul;16(7):318–322. doi: 10.1016/0167-5699(95)80144-8. [DOI] [PubMed] [Google Scholar]
  16. Schoemaker H., Bliss M., Yamamura H. I. Specific high-affinity saturable binding of [3H] R05-4864 to benzodiazepine binding sites in the rat cerebral cortex. Eur J Pharmacol. 1981 Apr 24;71(1):173–175. doi: 10.1016/0014-2999(81)90405-2. [DOI] [PubMed] [Google Scholar]
  17. Szegó J., Somogyi M., Papp E. Szemelvények a Grandaxin klinikai-farmakológiai és klinikai vizsgálataiból. Acta Pharm Hung. 1993 Mar;63(2):91–98. [PubMed] [Google Scholar]
  18. Wang J. K., Morgan J. I., Spector S. Benzodiazepines that bind at peripheral sites inhibit cell proliferation. Proc Natl Acad Sci U S A. 1984 Feb;81(3):753–756. doi: 10.1073/pnas.81.3.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zavala F. Benzodiazepines, anxiety and immunity. Pharmacol Ther. 1997 Sep;75(3):199–216. doi: 10.1016/s0163-7258(97)00055-7. [DOI] [PubMed] [Google Scholar]
  20. Zavala F., Haumont J., Lenfant M. Interaction of benzodiazepines with mouse macrophages. Eur J Pharmacol. 1984 Nov 27;106(3):561–566. doi: 10.1016/0014-2999(84)90059-1. [DOI] [PubMed] [Google Scholar]
  21. Zavala F., Masson A., Brys L., de Baetselier P., Descamps-Latscha B. A monoclonal antibody against peripheral benzodiazepine receptor activities the human neutrophil NADPH-oxidase. Biochem Biophys Res Commun. 1991 May 15;176(3):1577–1583. doi: 10.1016/0006-291x(91)90468-m. [DOI] [PubMed] [Google Scholar]
  22. Zisterer D. M., Williams D. C. Peripheral-type benzodiazepine receptors. Gen Pharmacol. 1997 Sep;29(3):305–314. doi: 10.1016/s0306-3623(96)00473-9. [DOI] [PubMed] [Google Scholar]

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