Amantadine

Amantadine treats parkinsonian dyskinesia as an muscarinic antagonist and acts as a noncompetitive NMDA antagonist. Amantadine was used as an antiviral drug used to treat and prevent influenza A infections. The antiviral mechanism of action is antagonism of the influenza A surface protein M2. M2 inhibition prevents viral shedding. Due to high levels of viral resistance to amantadine and other adamantanes, these drugs are no longer used against influenza A virus. Amantadine (trade names Gocovri, Symadine, and Symmetrel) is the organic compound 1-adamantylamine or 1-aminoadamantane (an adamantane backbone with an amino group substituted at one of the four methyne positions). Rimantadine is a closely related derivative of adamantane with similar biological properties (both target the M2 surface protein of influenza A virus). Amantadine is used to treat Parkinsons disease related dyskinesia and drug-induced parkinsonism syndromes. Amantadine may be used alone or combined with another anti-parkison or anticholinergic drug. The specific symptoms targeted by amatadine therapy are dyskinesia and rigidity. Levodopa and amantadine is a common combination. A 2003 Cochrane review concluded evidence inadequately proved the safety or efficacy of amantadine to treat dyskinesia. The World Health Organization in 2008 reported amantadine is not effective as a stand alone parkinsonian therapy. Amantadine was recommended for combination therapy with levodopa. Amantadine is no longer recommended for treatment or prophylaxis of influenza A in the United States. Amantadine has no effect preventing or treating influenza B infections. The Centers for Disease Control found 100% of seasonal H3N2 and 2009 pandemic flu samples were resistant to adamantanes (amantadine and rimantidine) during the 2008-2009 flu season. The CDC guidelines updated to recommend only neuraminidase inhibitors for influenza treatment and prophylaxis. The CDC currently recommends against amantadine and rimantadine to treat influenza A infections. Similarly, the 2011 World Health Organization virology report showed all tested H1N1 influenza A viruses were resistant to amantadine. Current WHO guidelines recommend against use of M2 inhibitors for influenza A. The continued high rate of resistance observed in laboratory testing of influenza A has reduced the priority of M2 resistance testing until further notice.