Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1982 Dec;22(6):1031–1036. doi: 10.1128/aac.22.6.1031

Tromantadine: inhibitor of early and late events in herpes simplex virus replication.

K S Rosenthal, M S Sokol, R L Ingram, R Subramanian, R C Fort
PMCID: PMC185716  PMID: 6297383

Abstract

Unlike amantadine (1-adamantanamine), tromantadine (N-1-adamantyl-N-[2-(dimethyl amino)ethoxy]acetamide hydrochloride) inhibits herpes simplex virus type 1 (KOS strain)-induced cytopathic effect and virus replication with limited toxicity to the cells. Vero and HEp-2 cells tolerated up to 2 mg of tromantadine per 2 X 10(6) cells for 24-, 48-, or 96-h incubation periods with little change in cell morphology. Treatment of the cells with 10 to 50 micrograms of tromantadine reduced herpes simplex virus-induced cytopathic effect. Treatment with 100 to 500 micrograms of tromantadine inhibited herpes simplex virus-induced cytopathic effect and reduced virus production. Complete inhibition of virus production was observed with treatments of 500 micrograms to 1 mg. The antiherpetic activity of tromantadine was dependent upon the viral inoculum size and the time of addition of the compound with respect to infection. Virion synthesis and viral polypeptide synthesis were inhibited by addition of tromantadine at the time of infection or 4 h postinfection. The results are consistent with tromantadine inhibition of an early event in herpes simplex virus infection, before macromolecular synthesis, and a late event, such as assembly or release of virus.

Full text

PDF
1031

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahumada M. Zur Wirksamkeit von Tromantadine bei Herpes simplex. Doppelblindstudie. Ther Ggw. 1977 Jan;116(1):100–108. [PubMed] [Google Scholar]
  2. Appleyard G. Amantadine-resistance as a genetic marker for influenza viruses. J Gen Virol. 1977 Aug;36(2):249–255. doi: 10.1099/0022-1317-36-2-249. [DOI] [PubMed] [Google Scholar]
  3. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  4. Borelli S., Gehrken H. Therapeutische Erfahrungen bei Herpes simplex-Erkrankungen mit Tromantadine HCl im Doppelblindversuch. Schweiz Rundsch Med Prax. 1976 Jan 27;65(4):108–110. [PubMed] [Google Scholar]
  5. Dreesman G. R., Benyesh-Melnick M. Spectrum of human cytomegalovirus complement-fixing antigens. J Immunol. 1967 Dec;99(6):1106–1114. [PubMed] [Google Scholar]
  6. Fanta D. Behandlung des Herpes simplex mit Tromantadin-hydrochlorid. Wien Med Wochenschr. 1976 May 21;126(20-22):315–317. [PubMed] [Google Scholar]
  7. Fenwick M. L., Walker M. J. Suppression of the synthesis of cellular macromolecules by herpes simplex virus. J Gen Virol. 1978 Oct;41(1):37–51. doi: 10.1099/0022-1317-41-1-37. [DOI] [PubMed] [Google Scholar]
  8. Hutter M. H., Schmidt R. Behandlung herpetischer Dermatosen. Erfahrungen im Zentral-Sanitätsbereich. ZFA (Stuttgart) 1978 Feb 10;54(4):243–245. [PubMed] [Google Scholar]
  9. Koff W. C., Elm J. L., Jr, Halstead S. B. Inhibition of dengue virus replication by amantadine hydrochloride. Antimicrob Agents Chemother. 1980 Jul;18(1):125–129. doi: 10.1128/aac.18.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kousoulas K. G., Person S., Holland T. C. Timing of some of the molecular events required for cell fusion induced by herpes simplex virus type 1. J Virol. 1978 Sep;27(3):505–512. doi: 10.1128/jvi.27.3.505-512.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. LaMontagne J. R., Galasso G. J. From the National Institutes of Health. Report of a workshop on clinical studies of the efficacy of amantadine and rimantadine against influenza vireus. J Infect Dis. 1978 Dec;138(6):928–931. doi: 10.1093/infdis/138.6.928. [DOI] [PubMed] [Google Scholar]
  12. Maxfield F. R., Willingham M. C., Davies P. J., Pastan I. Amines inhibit the clustering of alpha2-macroglobulin and EGF on the fibroblast cell surface. Nature. 1979 Feb 22;277(5698):661–663. doi: 10.1038/277661a0. [DOI] [PubMed] [Google Scholar]
  13. May G., Peteri D. Synthese und Prüfung von Adamantan-Abkömmlingen als Virustatika. Arzneimittelforschung. 1973 May;23(5):718–721. [PubMed] [Google Scholar]
  14. Morse L. S., Pereira L., Roizman B., Schaffer P. A. Anatomy of herpes simplex virus (HSV) DNA. X. Mapping of viral genes by analysis of polypeptides and functions specified by HSV-1 X HSV-2 recombinants. J Virol. 1978 May;26(2):389–410. doi: 10.1128/jvi.26.2.389-410.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Osdoby P., Caplan A. I. The possible differentiation of osteogenic elements in vitro from chick limb mesodermal cells. I. Morphological evidence. Dev Biol. 1976 Sep;52(2):283–299. doi: 10.1016/0012-1606(76)90246-3. [DOI] [PubMed] [Google Scholar]
  16. Peteri D., Sterner W. Chemie und Toxikologie einer neuen antiviralen Substanz: N-(1-Adamantyl)-2-(2-dimethylamino-äthoxy)-acetamid-HCl. 1. Arzneimittelforschung. 1973 Apr;23(4):577–581. [PubMed] [Google Scholar]
  17. Richman D. D., Yazaki P., Hostetler K. Y. The intracellular distribution and antiviral activity of amantadine. Virology. 1981 Jul 15;112(1):81–90. doi: 10.1016/0042-6822(81)90614-0. [DOI] [PubMed] [Google Scholar]
  18. Rothman J. E., Fine R. E. Coated vesicles transport newly synthesized membrane glycoproteins from endoplasmic reticulum to plasma membrane in two successive stages. Proc Natl Acad Sci U S A. 1980 Feb;77(2):780–784. doi: 10.1073/pnas.77.2.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Skehel J. J., Hay A. J., Armstrong J. A. On the mechanism of inhibition of influenza virus replication by amantadine hydrochloride. J Gen Virol. 1978 Jan;38(1):97–110. doi: 10.1099/0022-1317-38-1-97. [DOI] [PubMed] [Google Scholar]
  20. Welsh R. M., Trowbridge R. S., Kowalski J. B., O'Connell C. M., Peau C. J. Amantadine hydrochloride inhibition of early and late stages of lymphocytic choriomenigitis virus-cell interactions. Virology. 1971 Sep;45(3):679–686. [PubMed] [Google Scholar]
  21. Winkler A. Die Behandlung herpetischer Dermatosen mit einem neuartigen Virustatikum. Med Welt. 1973 Jun 15;24(24):1024–1027. [PubMed] [Google Scholar]
  22. de Duve C., de Barsy T., Poole B., Trouet A., Tulkens P., Van Hoof F. Commentary. Lysosomotropic agents. Biochem Pharmacol. 1974 Sep 15;23(18):2495–2531. doi: 10.1016/0006-2952(74)90174-9. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES