M2 Blockers (adamantanes)

The M2 blockers are the ‘older’ anti-flu medications, amantidine and rimantidine. Amantadine is used to treat Parkinson’s disease, and its anti-flu properties were first discovered when elderly people taking it for that indication failed to get flu when flu was rampant in their nursing homes. Rimantidine is a chemically related compound that has fewer side effects and is also effective against flu. The mechanism of action of these drugs is explained in Influenza Primer II. These drugs are considerably easier to manufacture and are far cheaper than the Neuriminidase Inhibitors.

Unfortunately, the H5N1 flu strains so far affecting humans in Southeast Asia are resistant to both of these anti-influenza medications. While it is possible this resistance developed as the result of farmers feeding sub-therapeutic doses of amantidine on poultry farms in China, the amantidine-resistant strains are primarily found in Vietnam and Thailand. Many of the H5N1 strains found in birds in China are not resistant to these drugs. However resistance develops rapidly, sometimes after only two or three days of treatment, so the use of these drugs in a pandemic is unclear even if the infecting virus is initially sensitive.

Medical journals citing M2 Blocker resistance of H5N1

  • Moscona, A. (2005). Neuraminidase Inhibitors for Influenza. N Engl J Med 353: 1363-1373
    The adamantanes interfere with viral uncoating inside the cell. They are effective only against influenza A and are associated with several toxic effects and with rapid emergence of drug-resistant variants. Adamantane-resistant isolates of influenza A are genetically stable, can be transmitted to susceptible contacts, are as pathogenic as wild-type virus isolates, and can be shed for prolonged periods in immunocompromised patients taking the drug. This potential for the development of resistance especially limits the use of the adamantanes for the treatment of influenza, although the drugs still have a place in planning for prophylaxis during an epidemic.
  • K. S. Li et al. Genesis of a Highly Pathogenic and Potentially Pandemic H5 N1 Influenza Virus in Eastern Asia. Nature 430 (July 2004): 20913.
  • Yuen KY, Wong SS Human infection by avian influenza A H5N1. Hong Kong Med J. 2005 Jun;11(3):189-99.
    The present circulating genotype Z is intrinsically resistant to amantadine and rimantadine.
  • Trampuz A, Prabhu RM, Smith TF, Baddour LM. Avian influenza: a new pandemic threat? Mayo Clin Proc. 2004 Apr;79(4):523-30; quiz 530.
    The H5N1 strains are resistant to amantadine and rimantadine but are susceptible to neuraminidase inhibitors, which can be used for treatment and prophylaxis.
  • Wainright PO, Perdue ML, Brugh M, Beard CW. Amantadine resistance among hemagglutinin subtype 5 strains of avian influenza virus. Avian Dis. 1991 Jan-Mar;35(1):31–9.
    These results demonstrate that amantadine resistance is widespread among avian influenza viruses of the H5 subtype, that drug sensitivity in cell culture does not necessarily reflect responses to amantadine in ovo and in vivo, and, as previously found, amantadine-resistant derivatives of H5 strains may be isolated from birds protected by the drug.
  • McKimm-Breschkin JL. Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance. Treat Respir Med. 2005;4(2):107–16.
    While amantadine and rimantadine have been available for the treatment of influenza in some countries for several years, they are only effective against influenza A viruses, they can have neurological and gastrointestinal adverse effects, and resistant virus is rapidly generated.
Page last modified on October 10, 2006, at 08:43 PM by pogge