approval for prophylactic use for influenza a in 1976. during the 1980 influenza a epidemic, the first amantadine-resistance influenza viruses were reported. the frequency of amantadine resistance among influenza a (h3n2) viruses from 1991 and 1995 was as low as 0.8%. in 2004 the resistance frequency increased to 12.3%. a year later resistance increase significantly to 96%, 72%, and 14.5% in china, south korea, and the united states, respectively. by 2006, 90.6% of h3n2 strains and 15.6% of h1n1 were amantadine-resistant. a majority of the amantadine-resistant h3n2 isolates (98.2%) were found to contain an s31n mutation in the m2 transmembrane domain that confers resistance to amantadine. currently, adamantane resistance is high among circulating influenza a viruses. thus, they are no longer recommended for treatment of influenza a. parkinson's disease an incidental finding in 1969 prompted investigations about amantadine's effectiveness for treating symptoms of parkinson's disease. a woman with parkinson's disease was prescribed amantadine to treat her influenza infection and reported her cogwheel rigidity and tremors improved. she also reported that her symptoms worsened after she finished the course of amantadine. the published case report was not initially corroborated by any other instances by the medical literature or manufacturer data. a team of researchers looked at a group of ten patients with parkinson's disease and gave them amantadine. seven of the ten patients showed improvement, which was convincing evidence for the need of a clinical trial, which included 163 patients with parkinson's disease and 66% experienced subjective or objective reduction of symptoms with a maximum daily dose of 200 mg. additional studies followed patients for greater lengths of time and in different combinations of neurological drugs. it was found to be a safe drug that could be used over long periods of time with few side effects as monotherapy or in combination with l-dopa or anti-cholinergic drugs. by april 1973, the u.s. food and drug administration approved amantadine for use in the treatment of parkinson's disease. in 2017, the u.s. food and drug administration approved the use of amantadine in an extended release formulation for the treatment of dyskinesia, an adverse effect of levodopa in people with parkinson's disease. veterinary misuse in 2005, chinese poultry farmers were reported to have used amantadine to protect birds against avian influenza. in western countries and according to international livestock regulations, amantadine is approved only for use in humans. chickens in china have received an estimated 2.6 billion doses of amantadine. avian flu (h5n1) strains in china and southeast asia are now resistant to amantadine, although strains circulating elsewhere still seem to be sensitive. if amantadine-resistant strains of the virus spread, the drugs of choice in an avian flu outbreak will probably be restricted to neuraminidase inhibitors oseltamivir and zanamivir which block the action of viral neuraminidase enzyme on the surface of influenza virus particles. however, there is an increasing incidence of oseltamivir resistance in circulating influenza strains (e.g., h1n1), highlighting the need for new anti-influenza therapies. in september 2015, the u.s. food and drug administration announced the recall of dingo chip twists "chicken in the middle" dog treats because the product has the potential to be contaminated with amantadine.