Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1980 Feb;17(2):109–114. doi: 10.1128/aac.17.2.109

Effect of treatment with 1-beta-D-arabinofuranosylthymine of experimental encephalitis induced by herpes simplex virus in mice.

H Machida, M Ichikawa, A Kuninaka, M Saneyoshi, H Yoshino
PMCID: PMC283742  PMID: 7387135

Abstract

1-beta-D-Arabinofuranosylthymine (ara-T) was examined for its therapeutic efficacy against encephalitis in mice inoculated intracerebrally with herpes simplex virus. Intraperitoneal treatment with 100 mg of ara-T per kg twice daily for 4.5 days was as effective as treatment with 50 mg of arabinosyladenine 5'-monophosphate per kg. Under the same conditions, doses of 5-iododeoxyuridine or arabinosylcytosine (50 mg/kg each) were not effective. Even when the virus inoculum was as high as 320 or 3,200 50% lethal doses, ara-T increased the life span significantly. Oral treatment with 27 mg of ara-T per kg produced a modest increase in the mean survival time, equal to that of 50 mg of ara-T per kg administered intraperitoneally or subcutaneously. A single dose of ara-T, 800 mg/kg intraperitoneally or 400 mg/kg orally, was effective. The 50% lethal dose of ara-T administered intraperitoneally and that administered orally were more than 10 and 15 g/kg, respectively. The therapeutic indexes (maximal tolerated dose divided by minimal effective dose) in multiple intraperitoneal treatments and in multiple oral treatments were estimated to be more than 25 and 100, respectively.

Full text

PDF
109

Selected References

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

  1. Allen L. B., Sidwell R. W. Target-organ treatment of neurotropic virus diseases: efficacy as a chemotherapy tool and comparison of activity of adenine arabinoside, cytosine arabinoside, idoxuridine, and trifluorothymidine. Antimicrob Agents Chemother. 1972 Sep;2(3):229–233. doi: 10.1128/aac.2.3.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aswell J. F., Allen G. P., Jamieson A. T., Campbell D. E., Gentry G. A. Antiviral activity of arabinosylthymine in herpesviral replication: mechanism of action in vivo and in vitro. Antimicrob Agents Chemother. 1977 Aug;12(2):243–254. doi: 10.1128/aac.12.2.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aswell J. F., Gentry G. A. Cell-dependent antiherpesviral activity of 5-methylarabinosylcytosine, an intracellular ara-T donor. Ann N Y Acad Sci. 1977 Mar 4;284:342–350. doi: 10.1111/j.1749-6632.1977.tb21969.x. [DOI] [PubMed] [Google Scholar]
  4. Cheng Y. C. A rational approach to the development of antiviral chemotherapy: alternative substrates of herpes simplex virus Type 1 (HSV-1) and Type 2 (HSV-2) thymidine kinase (TK). Ann N Y Acad Sci. 1977 Mar 4;284:594–598. doi: 10.1111/j.1749-6632.1977.tb21992.x. [DOI] [PubMed] [Google Scholar]
  5. Davis W. B., Oakes J. E., Taylor J. A. Effect of treatment with 5-ethyl-2'-deoxyuridine on herpes simplex virus encephalitis in normal and immunosuppressed mice. Antimicrob Agents Chemother. 1978 Nov;14(5):743–748. doi: 10.1128/aac.14.5.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. De Clercq E., Descamps J., De Somer P., Barr P. J., Jones A. S., Walker R. T. (E)-5-(2-Bromovinyl)-2'-deoxyuridine: a potent and selective anti-herpes agent. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2947–2951. doi: 10.1073/pnas.76.6.2947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dowdle W. R., Nahmias A. J., Harwell R. W., Pauls F. P. Association of antigenic type of Herpesvirus hominis with site of viral recovery. J Immunol. 1967 Nov;99(5):974–980. [PubMed] [Google Scholar]
  8. Gentry G. A., Aswell J. F. Inhibition of herpes simplex virus replication by araT. Virology. 1975 May;65(1):294–296. doi: 10.1016/0042-6822(75)90034-3. [DOI] [PubMed] [Google Scholar]
  9. Kaufman H. E., Varnell E. D., Centifanto Y. M., Rheinstrom S. D. Effect of 9-(2-hydroxyethoxymethyl)guanine on herpesvirus-induced keratitis and iritis in rabbits. Antimicrob Agents Chemother. 1978 Dec;14(6):842–845. doi: 10.1128/aac.14.6.842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klein R. J., Friedman-Kien A. E., DeStefano E. Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine. Antimicrob Agents Chemother. 1979 May;15(5):723–729. doi: 10.1128/aac.15.5.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kurtz S. M., Fitzgerald J. E., Schardein J. L. Comparative animal toxicology of vidarabine and its 5'-monophosphate. Ann N Y Acad Sci. 1977 Mar 4;284:6–8. doi: 10.1111/j.1749-6632.1977.tb21931.x. [DOI] [PubMed] [Google Scholar]
  12. Lefkowitz E., Worthington M., Conliffe M. A., Baron S. Comparative effectiveness of six antiviral agents in Herpes simplex type 1 infection of mice. Proc Soc Exp Biol Med. 1976 Jul;152(3):337–342. doi: 10.3181/00379727-152-39392. [DOI] [PubMed] [Google Scholar]
  13. Machida H., Sakata S., Kuninaka A., Yoshino H., Nakayama C., Saneyoshi M. In vitro antiherpesviral activity of 5-alkyl derivatives of 1-beta-D-arabinofuranosyluracil. Antimicrob Agents Chemother. 1979 Aug;16(2):158–163. doi: 10.1128/aac.16.2.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller R. L., Iltis J. P., Rapp F. Differential effect of arabinofuranosylthymine of the replication of human herpesviruses. J Virol. 1977 Sep;23(3):679–684. doi: 10.1128/jvi.23.3.679-684.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Müller W. E., Zahn R. K., Arendes F., Falke D. Phosphorylation of arabinofuranosylthymine in non-infected and herpesvirus (TK+ and TK-)-infected cells. J Gen Virol. 1979 May;43(2):261–271. doi: 10.1099/0022-1317-43-2-261. [DOI] [PubMed] [Google Scholar]
  16. Müller W. E., Zahn R. K., Maidhof A., Beyer R., Arendes J. Arabinosyl nucleosides. XII. Influence of arabino-furanosylthymine on growth of L5178y cells. Chem Biol Interact. 1978 Nov;23(2):141–150. doi: 10.1016/0009-2797(78)90001-7. [DOI] [PubMed] [Google Scholar]
  17. NICHOLS W. W. IN VITRO CHROMOSOME BREAKAGE INDUCED BY ARABINOSYLADENINE IN HUMAN LEUKOCYTES. Cancer Res. 1964 Sep;24:1502–1505. [PubMed] [Google Scholar]
  18. Nahmias A. J., Roizman B. Infection with herpes-simplex viruses 1 and 2. 3. N Engl J Med. 1973 Oct 11;289(15):781–789. doi: 10.1056/NEJM197310112891505. [DOI] [PubMed] [Google Scholar]
  19. Olson L. C., Buescher E. L., Artenstein M. S., Parkman P. D. Herpesvirus infections of the human central nervous system. N Engl J Med. 1967 Dec 14;277(24):1271–1277. doi: 10.1056/NEJM196712142772401. [DOI] [PubMed] [Google Scholar]
  20. Prusoff W. H., Ward D. C. Nucleoside analogs with antiviral activity. Biochem Pharmacol. 1976 Jun 1;25(11):1233–1239. doi: 10.1016/0006-2952(76)90083-6. [DOI] [PubMed] [Google Scholar]
  21. Puliafito C. A., Robinson N. L., Albert D. M., Pavan-Langston D., Lin T. S., Ward D. C., Prusoff W. H. Therapy of experimental herpes simplex keratitis in rabbits with 5-lodo-5'-amino-2',5'-dideoxyuridine (39882). Proc Soc Exp Biol Med. 1977 Oct;156(1):92–96. doi: 10.3181/00379727-156-39882. [DOI] [PubMed] [Google Scholar]
  22. Revankar G. R., Huffman J. H., Allen L. B., Sidwell R. W., Robins R. K., Tolman R. L. Synthesis and antiviral activity of certain 5'-monophosphates of 9-D-arabinofuranosyladenine and 9-D-arabinofuranosylhypoxanthine. J Med Chem. 1975 Jul;18(7):721–726. doi: 10.1021/jm00241a016. [DOI] [PubMed] [Google Scholar]
  23. Ross A. H., Julia A., Balakrishnan C. Toxicity of adenine arabinoside in humans. J Infect Dis. 1976 Jun;133 (Suppl):A192–A198. doi: 10.1093/infdis/133.supplement_2.a192. [DOI] [PubMed] [Google Scholar]
  24. Schaeffer H. J., Beauchamp L., de Miranda P., Elion G. B., Bauer D. J., Collins P. 9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Nature. 1978 Apr 13;272(5654):583–585. doi: 10.1038/272583a0. [DOI] [PubMed] [Google Scholar]
  25. Sidwell R. W., Allen L. B., Huffman J. H., Khwaja T. A., Tolman R. L., Robins R. K. Anti-DNA virus activity of the 5'-nucleotide and 3',5'-cyclic nucleotide of 9-beta-D-arabinofuranosyladenine. Chemotherapy. 1973;19(6):325–340. doi: 10.1159/000221473. [DOI] [PubMed] [Google Scholar]

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

RESOURCES