Vet Med - Czech, 2001, 46(9):244-256 | DOI: 10.17221/7884-VETMED
Amantadine: an antiviral and antiparkinsonian agentInformation
- 1 University of Veterinary Medicine, Košice, Slovak Republic
- 2 University of P.J. Šafárik, Košice, Slovak Republic
Amantadine is an antiviral agent that specifically inhibits influenza A virus replication at a micromolar concentration. This drug is also very effective in the treatment of human Parkinson's disease. Other important clinical applications of this agent have been studied recently, ranging from viral infections, e.g. herpes, herpes zoster neuralgia to granulomatosis and from neuroleptic extrapyramidal movement disease to depression and cocain dependence. Biological and pharmacological activities of amantadine presented in this paper are focused on the explanation of the mechanism of amantadine antiviral and antiparkinsonian effects and on general use of this agent in medicine.
Keywords: influenza A; M2 protein; chemotherapy; chemoprophylaxis; Parkinson's disease
Published: September 30, 2001 Show citation
References
- Aoki F. Y., Sitar S. (1988): Clinical pharmacokinetics of amantadine hydrochloride. Clin. Pharmacokinet, 14, 35-51.
Go to original source...
Go to PubMed...
- Bauer R., McHenry J. (1974): Comparison of amantadine, placebo, and levodopa in Parkinson's disease. Neurology, 24, 715-720.
Go to original source...
Go to PubMed...
- Beran J. (1999): Chráni nás očkovanie proti chrípke? Forum Med., 1, 30-38.
- Blake G.J. (1990): Amantadine for influenza A. Nursing, 90, 21.
Go to original source...
Go to PubMed...
- Boreko E.I., Pavlova N.I., Votyakov V.I. (1996): Antiviral effects of carbocyclic compounds in different concentrations. Vopr. Virusol., 3, 129-133.
- Carrasco L. (1995): Modification of membrane permeability by animal viruses. Adv. Virus Res., 45, 61-111.
Go to original source...
Go to PubMed...
- Chambers T.M., Shortridge K.F., Li P.H. (1994): Rapid diagnosis of equine influenza by the Directigen FLU-A enzyme immunoassay. Vet. Rec., 135, 275-279.
Go to original source...
Go to PubMed...
- Chambers T.M., Holland R.E., Lai A.C.K. (1995a): Equine influenza - Current veterinary perspectives, Part 1. Equine Pract., 17, 19-23.
- Chambers T.M., Holland R.E., Lai A.C.K. (1995b): Equine influenza - Current veterinary perspectives, Part 2. Equine Pract., 17, 26-30.
- Čiampor F. (1993): Electron microscopy and confocal scanning imaging system in the process of intracellular transport and conformational changes of virus structural proteins. In: Proceedings of Multinational Congress on Electron Microscopy, Parma. 445-449.
- Čiampor F. (1997): Modifikácia konformácie glykoproteínov a permeability membrán iónovými kanálmi kódovanými vírusmi. XIV. Biologické dni, Praha, KP9/1.
- Čiampor F., Bayley P.M., Nermut M.V., Hirst E.M.A., Sugrue R.J., Hay A.J. (1992a): Evidence that the amantadineinduced, M2-mediated conversion of influenza A virus hemagglutinin to the low pH conformation occurs in an acidic trans golgi compartment. Virology, 188, 14-24.
Go to original source...
Go to PubMed...
- Čiampor F., Thompson C.A., Grambas S., Hay A.J. (1992b): Regulation the of pH by the M2 protein of influenza A viruses. Virus Res., 22, 247-258.
Go to original source...
Go to PubMed...
- Čiampor F., Varečková E., Kostolanský F. (1998): A16. Ortomyxovírusy (Čeľaď Ortomyxoviridae). In: Žemla J., Čiampor F., Labuda M. (eds.): Špeciálna virológia. Slovac Academic Press, Bratislava. 99-106.
- Danielczyk W. (1995): Twenty-five years of amantadine therapy in Parkinson's disease. J. Neural. Transm., 46 (Suppl.), 399-405.
- Daniels R.S., Downie J.C., Hay A.J., Knossow M., Skehel J.J., Wang M.L., Wiley D.C. (1985): Fusion mutants of the influenza virus haemagglutinin glycoprotein. Cell, 40, 431-439.
Go to original source...
Go to PubMed...
- De Duve C., de Barsy T., Poole B., Trouet A., Tulkens P., van Hoof F. (1974): Lysosomotropic agents. Biochem. Pharmacol., 23, 2495-2531.
Go to original source...
Go to PubMed...
- Dolin R., Reichman R. C., Madore P., Maynard R., Linton P., Webber-Jones J. (1982): A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. New. Engl. J. Med., 10, 580-583.
Go to original source...
Go to PubMed...
- Douglas, Jr R. G. (1990): Antimicrobial agents. In: Goodman Gilman A., Rall T.W., Nies A..S., Taylor P. (eds.): Goodman and Gilman's the Pharmacological Basis of Therapeutics. Pergamon Press, New York. Chapter 51.
Go to original source...
- Duff K.C., Kelly S.M., Price N.C., Bradshaw J.P. (1992): The secondary structure of influenza A M2 transmembrane domain A circular dichroism study. FEBS, 311, 256-258.
Go to original source...
Go to PubMed...
- Duff K.C., Cudmore A.J., Bradshaw J P. (1993): The location of amantadine hydrochloride and free base within phospholipid multilayers: a neutron and X-ray diffraction study. Biochim. Biophys. Acta, 1145, 149-156.
Go to original source...
Go to PubMed...
- Duvoisin R.C. (1991): Parkinson's Disease. Raven Press, New York. Chapter 6, 75.
- Ewart G.D., Sutherland T., Gage P.W., Cox G.B. (1996): The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels. J. Virol., 70, 7108-7115.
Go to original source...
Go to PubMed...
- Factor S.A., Molho E.S., Brown D.L. (1998): Acute delirium after withdrawal of amantadine in Parkinson's disease. Neurology, 50, 1456-1458.
Go to original source...
Go to PubMed...
- Gandhi CH.S., Shuck K., Lear J.D., Dieckmann G.R., Degrado W.F., Lamb R.A., Pinto L.H. (1999): Cu(II) inhibition of the proton translocation machinery of the influenza A virus M2 protein. J. Biol. Chem., 274, 5474-5482.
Go to original source...
Go to PubMed...
- Goldstein J.L., Brown M.S., Anderson R.G.W., Russell D.W., Schneier W.J. (1985): Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. Ann. Rev. Cell. Biol., 1, 1-39.
Go to original source...
Go to PubMed...
- Grelak R.P., Clark R., Stump J.M., Vernier V.G. (1970): Amantadine-dopamine interaction: possible mode of action in Parkinsonism. Sci., 169, 203-204.
Go to original source...
Go to PubMed...
- Greulich W., Fenger E. (1995): Amantadine in Parkinson's disease: pro and contra. J. Neural. Transm., 46 (Suppl.) 415-421.
- Hallensleben W., Zocher M., Staeheli P. (1997): Borna disease virus is not sensitive to amantadine. Arch. Virol., 142, 2043-2048.
Go to original source...
Go to PubMed...
- Hartshorne N.J., Harruff R.C., Logan B.K. (1995): Unexpected amantadine intoxication in the death of a trauma patient. Am. J. Forencis. Med. Pathol., 16, 340-343.
Go to original source...
Go to PubMed...
- Hay A.J. (1992): The action of adamantanamines against influenza A viruses: inhibition of the M2 ion channel protein. Semin.Virol., 3, 21-30.
- Hay A.J., Zambon M.C. (1984): Multiple actions of amantadine against influenza viruses. In: Becker Y. (ed.): Antiviral Drugs and Interferon: The Molecular Basis of their Activity. Martinus Nijhoff Publishing, Boston. 301-315.
Go to original source...
- Hay A.J., Wolstenholme A.J., Skehel J.J., Smith M.H. (1985): The molecular basis of the specific anti-influenza action of amantadine. EMBO J., 4, 3021-3024.
Go to original source...
Go to PubMed...
- Hayden F., Hoffman H., Spyker D. (1983): Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics. Antimicrob. Agents Chemother., 23, 458-464.
Go to original source...
Go to PubMed...
- Huber T.J., Dietrich D.E., Emrich H.M. (1999): Possible use of amantadine in depression. Pharmacopsychiatry, 32, 47-55.
Go to original source...
Go to PubMed...
- Hull D.J., Gilmore R., Lamb R.A. (1988): Integration of a small integral membrane protein, M2, of influenza virus into the endoplasmic reticulum: analysis of the internal signal-anchor domain of a protein with an ectoplasmic NH2 terminus. J. Cell Biol., 106, 1489-1498.
Go to original source...
Go to PubMed...
- Jáuregui I., Urrutia I., Gamboa P.M., Antépara I. (1997): Allergic contact dermatitis from tromantadine. Invest. Allergol. Clin. Immunol., 7, 260-261.
- Johnson R.G., Carty S.E., Scarpa A. (1981): Accumulation of amantadine by isolated chromaffin granules. Biochem. Pharmacol., 30, 763-769.
Go to original source...
Go to PubMed...
- König P., Chwatal K., Havelec L., Riedl F., Schubert H., Schultes H. (1996): Amantadine versus biperiden: A double-blind study of treatment efficacy in neuroleptic extrapyramidal movement disordes. Neuropsychobiology, 33, 80-84.
Go to original source...
Go to PubMed...
- Kornhuber J., Streifler M. (1992): Adamantanamine. In: Riederer P., Laux G.. Pöldinger W (eds.): Neuro-psychopharmaka. Bd. 5. Springer, Wien, New York. 59.
Go to original source...
- Kornhuber J., Retz W., Riederer P. (1995): Slow accumulation of psychotropic substances in the human brain. Relationship to therapeutic latency of neuroleptic and antidepressant drugs? J. Neural Transm., 46 (Suppl.), 315-323.
- Kovacs F.A., Cross T.A. (1997): Transmembrane four-helix bundle of influenza A M2 protein channel: Structural implications from helix tilt and orientation. Biophys. J., 73, 2511-2517.
Go to original source...
Go to PubMed...
- Kraus G.A., Zhang W., Fehr M.J, Petrich J.W., Wannemuehler Y., Carpenter S. (1996): Research at the interface between chemistry and virology: Development of a molecular flashlight. Chem. Rev., 96, 523-535.
Go to original source...
Go to PubMed...
- Kukol A., Adams P.D., Rice L.M., Brunger A.T., Arkin I.T. (1999): Experimentally based orientational refinement of membrane protein models: A structure for the influenza A M2 H+ channel. J. Mol. Biol., 286, 951-962.
Go to original source...
Go to PubMed...
- Lamb R.A., Zebedee S.L., Richardson C.D. (1985): Influenza virus M2 protein is an integral membrane protein expressed on the infected cell surface. Cell, 40, 627-633.
Go to original source...
Go to PubMed...
- Martín J., Navas S., Fernández M., Rico M., Pardo M., Quiroga J.A., Zahm F., Carreno V. (1999): In vitro effect of amantadine and interferon α-2a on hepatitis C virus markers in cultured peripheral blood mononuclear cells from hepatitis C virus-infected patients. Antivir. Res., 42, 59-70.
Go to original source...
Go to PubMed...
- Mellman I., Fuchs R., Helenius A. (1986): Acidification of the endocytic and exocytic pathways. Ann. Rev. Biochem., 55, 663-700.
Go to original source...
Go to PubMed...
- Monto A.S. (1994): Using antiviral agents to control outbreaks of influenza A infection. Geriatrics, 49, 30-34.
Go to PubMed...
- Nahata M.C., Brady M.T. (1986): Serum concentrations and safety of Rimantadine in paediatric patients. Eur. J. Clin. Pharmacol., 30, 719-722.
Go to original source...
Go to PubMed...
- Nair S.K., Christianson D.W. (1991): Unexpected pH-dependent conformation of His-64, the proton shuttle of carbonic anhydride II. J. Am. Chem. Soc., 113, 9455-9458.
Go to original source...
- Ohkuma S., Poole B. (1981): Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances. J. Cell. Biol., 90, 656-664.
Go to original source...
Go to PubMed...
- Oxford J.S. (1997): Amantadine in man and horse - can we learn from each other. Equine Vet. J., 29, 89-91.
Go to original source...
Go to PubMed...
- Parks G.D., Lamb R.A. (1991): Topology of eukaryotic Type I membrane proteins: importance of N-terminal positively charged residues flanking the hydrophobic domain. Cell, 64, 777-787.
Go to original source...
Go to PubMed...
- Perrin D.D., Hawkins I. (1972): Dissociation constant of the 1-aminoadamantane cation. Experientia, 28, 880.
Go to original source...
- Pfeiffer R.F. (1996): Amantadine-induced "Vocal" myoclonus. Movement Disord., 11, 104-106.
Go to original source...
Go to PubMed...
- Pinto L.H., Holsinger L.J., Lamb R.A. (1992): Influenza virus M2 protein has ion channel activity. Cell, 69, 517-528.
Go to original source...
Go to PubMed...
- Pinto L.H., Dieckmann G.R., Gandhi CH.S., Papworth C.G., Braman J., Shaughnessy M.A., Lear J.D., Lamb R.A., Degrado W.F. (1997): A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity. Proc. Natl. Acad. Sci. USA, 94, 11301-11306.
Go to original source...
Go to PubMed...
- Rees W.A., Harkins J.D., Woods W.E., Blouin R.A., Lu M., Fenger C., Holland R.E., Chambers T.M., Tobin T. (1997): Amantadine and equine influenza: pharmacology, pharmacokinetics and neurological effects in the horse. Equine Vet. J., 29, 104-110.
Go to original source...
Go to PubMed...
- Richman D.D., Yazaki P., Hostetler K.Y. (1981): The intracellular distribution and antiviral activity of amantadine. Virology, 112, 81-90.
Go to original source...
Go to PubMed...
- Ruigrok R.W.H., Hirst E.M.A., Hay A.J. (1991): The specific inhibition of influenza A virus maturation by amantadine: an electron microscopic examination. J. Gen. Virol., 72, 191-194.
Go to original source...
Go to PubMed...
- Sabó A. (1998): Ekológia vírusu chrípky rodu A a mechanizmy vzniku nových subtypov vírusu. Slov. Vet. Čas., 23, 4-19.
- Shimbo K., Brassard D., Lamb R., Pinto L. (1996): Ion selectivity and activation of the M2 ion channel of influenza virus. Biophys. J., 70, (3), 1335-1346.
Go to original source...
Go to PubMed...
- Schwab R., Poskanzer D., England A., Young R. (1972): Amantadine in Parkinson's disease. JAVMA, 222, 792- 795.
Go to original source...
- Silverman D.N., Lindskog S. (1988): The catalytic mechanism of carbonic anhydrase: Implications of a rate-limiting protolysis of water. Acc. Chem. Res., 21, 30-36.
Go to original source...
- Skehel J.J., Hay A.J., Armstrong J.A. (1978): On the mechanism of inhibition of influenza virus replication by amantadine hydrochloride. J. Gen. Virol., 38, 97-110.
Go to original source...
Go to PubMed...
- Smith J.P. (1996): Treatment of chronic hepatitis C with amantadine-hydrochloride. In: Ann. Meet. of Am. Gastroenter. Assoc. and Am. Ass. for Study of Liver Dis., May 19-22.
- Staničová J., Kovalčík L., Chinsky L., Miškovský P. (2001): Pre-resonance Raman and surface-enhanced Raman spectroscopy study of the complex of the antiviral and antiparkinsonian drug amantadine with histidine. Vib. Spectrosc., 25, 41-51.
Go to original source...
- Sugrue R.J., Hay A.J. (1991): Structural characteristics of the M2 protein of influenza A viruss: Evidence that it forms a tetrametric channel. Virology, 180, 617-624.
Go to original source...
Go to PubMed...
- Sugrue R.J., Bahadur G., Zambon M.C., Hall-Smith M., Douglas A.R., Hay A.J. (1990): Specific structural alteration of the influenza haemagglutinin by amantadine. EMBO J., 9, 3469-3476.
Go to original source...
Go to PubMed...
- Tamblyn S.E. (1997): Amantadine use in influenza outbreaks in long-term care facilities. Can. Med. Assoc. J., 157, 1573-1574.
- Van Laar T., Lammers G.J., Roos R.A.C., Gerritsen J.J., Meinders A.E. (1998): Antiparkinsonian drugs causing inappropriate antidiuretic hormone secretion. Movement Disord., 13, 176-178.
Go to original source...
Go to PubMed...
- Volchow N.D., Fowler J.S., Wolf A.P., Schyler D., Shiue C., Alpert R., Dewey S.L., Logan J., Bendriem B., Christman D., Hitzmann R., Henn F. (1990): Effects of chronic cocaine abuse on post-synaptic dopamine receptors. Am. J. Psychiatr., 147, 719-724.
Go to original source...
Go to PubMed...
- Von Heijne G. (1988): Transcending the impenetrable how proteins come to terms with membranes. Biochim. Biophys. Acta, 189, 239-242.
Go to original source...
Go to PubMed...
- Wang CH., Takeuchi K, Pinto L.H., Lamb R.A. (1993): Ion channel activity of influenza A virus M2 protein: Characterization of the amantadine block. J. Virol., 67, 5585- 5594.
Go to original source...
Go to PubMed...
- Zebedee S.L., Lamb R.A. (1988): Influenza A virus M2 protein: Monoclonal antibody restriction of virus growth and detection of M2 in virions. J. Virol., 62, 2762-2772.
Go to original source...
Go to PubMed...
- Zebedee S.L., Richardson C.D., Lamb R.A. (1985): Characterization of the influenza virus M2 integral membrane protein and expression at the infected-cell surface from cloned cDNA. J. Virol., 56, 502-511.
Go to original source...
Go to PubMed...
- Zeldowicz L.R., Huberman J. (1973): Long-term therapy of Parkinson's disease with amantadine, alone and combined with levodopa. Can. Med. Assoc. J., 109, 588-593.
Go to PubMed...
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY NC 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.