Amantadine and Its Derivatives

  • J. L. Schulman
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 61)


Amantadine hydrochloride (1-adamantanamine hydrochloride) was the first antiviral chemotherapeutic agent (1966) to be licensed for general use in the United States. However, despite the demonstrated efficacy of this compound in the prophylaxis (and more recently in the treatment) of influenza A virus infections, it has never been widely employed and its recommended use remains the subject of considerable controversy (Sabin 1978).


Influenza Virus Influenza Virus Infection Rubella Virus Influenza Virus Replication Amantadine Hydrochloride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Appleyard G (1977) Amantadine resistance as a genetic marker for influenza viruses. J Gen Virol 36: 249–255PubMedCrossRefGoogle Scholar
  2. Bleidner WE, Harmon JB, Hewes WE, Lynes TE, Herman EC (1965) Absorbtion distribution and excretion of amantadine hydrochloride. J Pharmacol Exp Ther 150: 484–490PubMedGoogle Scholar
  3. Bryans JT, Zent WW, Grunert RR, Boughton DC (1966) 1-Adamantanamine prophylaxis for experimentally induced A/equine 2 influenza virus infection. Nature 212:1542–1544Google Scholar
  4. Bryson YJ, Monahan C, Pollack M, Shields WD (1980) A prospective double-blind study of side effects associated with the administration of amantadine for influenza A prophylaxis. J Infect Dis 141: 543–547PubMedCrossRefGoogle Scholar
  5. Cochran KW, Maassab HF, Tsunoda A, Berlin BS (1965) Studies on the antiviral activity of amantadine hydrochloride. Ann NY Acad Sci 130: 432–439PubMedCrossRefGoogle Scholar
  6. Couch RB, Jackson GG (1976) Antiviral agents in influenza. Summary of Influenza Workshop VIII. J Infect Dis 134: 516–527PubMedCrossRefGoogle Scholar
  7. Davies WL, Grunert RR, Haff RF et al. (1964) Antiviral activity of 1-adamantanamine (amantadine). Science 144: 862–863PubMedCrossRefGoogle Scholar
  8. Dourmashkin RR, Tyrrell DJ (1974) Electron microscope evidence of the entry of influenza virus into susceptible cells. J Gen Virol 24: 129–141PubMedCrossRefGoogle Scholar
  9. Fenton RJ, Bessell C, Spilling CR, Potter CW (1977) The effects of peroral or local aerosal administration of 1-aminoadamantane hydrochloride (amantadine hydrochloride) on influenza infection of the ferret. J Antimicrob Chemother 3: 463–472PubMedCrossRefGoogle Scholar
  10. Galbraith AW, Oxford JS, Schild GC, Watson GL (1969) Protective effects of 1-adamantanamine hydrochloride on influenza A2 infections in the family environment. Lancet 2: 1026–1028PubMedCrossRefGoogle Scholar
  11. Galbraith AW, Oxford JS, Schild GC, Potter CW, Watson GI (1971) Therapeutic effect of 1-adamantanamine hydrochloride in naturally occurring influenza A2/Hong Kong infection. A controlled double-blind study. Lancet 2: 113–115Google Scholar
  12. Gailbraith AW, Schild GC, Potter CW, Watson GI (1973) The therapeutic effect of amantadine in influenza occurring during the winter of 1971–72 assessed by double-blind study. J Coll Gen Pract 23: 34–37Google Scholar
  13. Grunert RR, McGahen JW, Davies WL (1965) The in vitro activity of 1-adamantanamine (amantadine). Prophylactic and therapeutic value against influenza viruses. Virology 26: 262–269CrossRefGoogle Scholar
  14. Hayden FG, Hall WJ, Doublas RG (1980) Therapeutic effects of aerosolized amantadine in naturally acquired infection due to influenza virus. J Infect Dis 141: 535–542PubMedCrossRefGoogle Scholar
  15. Hoffman CE, Neumayer EM, Haff RF, Goldsby RA (1965) Mode of action of the antiviral activity amantadine in tissue culture. J Bacteriol 90: 623–628Google Scholar
  16. Kalninya VA, Indulen MK (1976) Effect of amantadine derivatives on the activity of orthomyxovirus RNA-dependent RNA polymerase. Acta Virol (Praha) (Engled) 20: 343–346Google Scholar
  17. Kato N, Eggers HJ (1969) Inhibition of uncoating of fowl plague virus by 1-adamantanamine hydrochloride. Virology 37: 632–641PubMedCrossRefGoogle Scholar
  18. Kitamato O (1971) Therapeutic effectiveness of amantadine hydrochloride in naturally occurring Hong Kong influenza double-blind studies. Jpn J Tuberc 17: 1–7Google Scholar
  19. Knight V, Fedson D, Baldini J, Douglas RG, Couch RB (1970) Amantadine therapy of epidemic influenza A2 ( Hong Kong ). Infect Immun 1: 200–204PubMedGoogle Scholar
  20. Koff WC, Knight V (1979) Effect of amantadine on influenza virus replication. Proc Soc Exp Biol Med 160: 246–253PubMedGoogle Scholar
  21. Little JW, Hall WJ, Douglas RG Jr, Hyde RW, Speers DM (1976) Amantadine effect on peripheral airways abnormalities in influenza–a study in 15 students with natural influenza infection. Ann Intern Med 85: 177–182PubMedGoogle Scholar
  22. Little JW, Hall WJ, Douglas RG Jr (1977) Small airways dysfunction in influenza virus infection. Therapeutic role and potential mode of action of amantadine. Ann NY Acad Sci 284: 106–117Google Scholar
  23. Lubeck MD, Schulman JL, Palese P (1978) Susceptibility of influenza A viruses to amantadine is influenced by the gene coding for M protein. J Virol 28: 710–716PubMedGoogle Scholar
  24. Maassab HF, Cochran KW (1964) Rubella virus inhibition in vitro by amantadine hydrochloride. Science 145: 1443–1444PubMedCrossRefGoogle Scholar
  25. Monto AS, Gunn RA, Bandyk MG, King CL (1979) Prevention of Russian influenza by amantadine. JAMA 241: 1003–1007PubMedCrossRefGoogle Scholar
  26. Neumayer EM, Haff RF, Hoffman CE (1965) Antiviral activity of amantadine hydrochloride in tissue culture and in ovo. Proc Soc Exp Biol Med 119: 393–396PubMedGoogle Scholar
  27. O’Donahue JM, Ray CG, Terry DW Jr, Beatty HN (1973) Prevention of nasocomial influenza infections with amantadine. Am J Epidemiol 97: 276–282Google Scholar
  28. Oxford JS (1977) Specific inhibitors of influenza related to the molecular biology of virus replication. In: Oxford JS (ed) Chemoprophylaxis and virus infections of the respiratory tract, vol I. CRC Press, Cleveland, Ohio, pp 140–187Google Scholar
  29. Oxford JS, Schild GC (1967) The evaluation of antiviral compounds for rubella virus using organ cultures. Arch Ges Virusforsch 22: 349–356PubMedCrossRefGoogle Scholar
  30. Oxford JS, Logan IS, Potter CW (1970) Passage of influenza strains in the presence of aminoadamantane. Ann NY Acad Sci 173: 300–313CrossRefGoogle Scholar
  31. Pfau CV, Trowbridge RS, Welsh RM, Staneck LD, O’Connell CM (1972) Arenaviruses: inhibition by amantadine hydrochloride. J Gen Virol 14: 209–211PubMedCrossRefGoogle Scholar
  32. Plotkin SA (1965) Inhibition of rubella virus by amantadine. Arch Ges Virusforsch 16: 438–442PubMedCrossRefGoogle Scholar
  33. Sabin AB (1978) Amantadine and influenza: evaluation of conflicting reports. J Infect Dis 138: 557–566PubMedCrossRefGoogle Scholar
  34. Schild GC, Sutton RN (1965) Inhibition of influenza viruses in vitro and in vivo by 1-adamantanamine hydrochloride. Br J Exp Pathol 46: 263–273PubMedGoogle Scholar
  35. Schulman JL (1968) Effect of 1-amantanamine hydrochloride (amantadine CHI) on transmission of influenza virus infection in mice. Proc Soc Exp Biol Med 128: 1173–1178Google Scholar
  36. Skehel JJ, Hay AJ, Armstrong JA (1977) On the mechanism of inhibition of influenza virus replication by amantadine hydrochloride. J Gen Virol 38: 97–110CrossRefGoogle Scholar
  37. Squires SL (1970) The evaluation of compounds against influenza viruses. Ann NY Acad Sci 173: 229–248CrossRefGoogle Scholar
  38. Stephenson JA, Artenstein MS, Parkman PD, Buescher EL, Druzd AD (1965) Effect of amantadine hydrochloride on rubella virus infection in the rhesus monkey. Antimicrob Agents Chemother 548–552Google Scholar
  39. Togo Y, Hornick RB, Felitti VG, Kaufman ML, Dawkins AT, Kilpe VE, Claghorn JL (1970) Evaluation of therapeutic efficacy of amantadine in patients with naturally occurring A2 influenza. JAMA 211: 1149–1156PubMedCrossRefGoogle Scholar
  40. Van Voris LP, Betts RF, Hayden FG, Christmas WA, Douglas RG Jr (to be published) Oral amantadine and rimantadine therapy of naturally occurring influenza A/USSR/77 H1N1. JAMAGoogle Scholar
  41. Vernier VG, Harmon JB, Stump JM, Lynes TE, Marvel JP, Smith DH (1969) The toxicologic and pharmacologic properties of amantadine hydrochloride. Toxicol Appl Pharmacol 15: 642–665PubMedCrossRefGoogle Scholar
  42. Welsh RM, Trowbridge RS, Kowalski JB, O’Connell CM, Pfau CJ (1971) Amantadine hydrochloride inhibition of early and late stages lymphocytic choriomeningitis virus-cell interactions. Virology 45:679–686Google Scholar
  43. Walker JS, Stephen ES, Spertzel RO (1976) Small particle aerosols of antiviral compounds in treatment of type A influenza in pneumonia in mice. J Infect Dis [Suppl A] 133: 140 - A144CrossRefGoogle Scholar
  44. Welsh RM, Trowbridge RS, Kowalski JB, O’Connell CM, Pfau CJ (1971) Amantadine hydrochloride inhibition of early and late stages lymphocytic choriomeningitis virus-cell interactions. Virology 45: 679–686CrossRefGoogle Scholar
  45. Wingfield WL, Pollack D, Grunert RP (1969) Therapeutic efficacy of amantadine HC1 and rimantadine HC1 in naturally occurring influenza A2 respiratory illness in man. N Engl J Med 281: 579–584PubMedCrossRefGoogle Scholar
  46. Zvonarjev AY, Ghendon YZ (1980) Influence of membrane (M) protein of influenza A virus virion transcriptase activity in vitro and its susceptibility to amantadine. J Virol 33: 583–586PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1982

Authors and Affiliations

  • J. L. Schulman

There are no affiliations available

Personalised recommendations