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.

Parkinsons disease
An incidental finding in 1969 prompted investigations about amantadines effectiveness for treating symptoms of Parkinsons disease. A woman with Parkinsons 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 Parkinsons 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 Parkinsons 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.
Amantadine is contraindicated in persons with end stage kidney disease, given that the drug is cleared by the kidneys. It should also be taken with caution in those with enlarged prostates or glaucoma, due to its anticholinergic effects. Live attenuated vaccines are contraindicated while taking amantadine, as it may limit the efficacy of the administered vaccine. Chemical structure
Amantadine (brand names Gocovri, Symadine, and Symmetrel) is the organic compound 1-adamantylamine or 1-aminoadamantane, which consists of an adamantane backbone with an amino group substituted at one of the four methyne positions. Rimantadine is a closely related adamantane derivative with similar biological properties; both target the M2 proton channel of influenza A virus. Mechanism of action
Parkinsons disease
The mechanism of its antiparkinsonian effect is poorly understood. Amantadine is a weak antagonist of the NMDA-type glutamate receptor, increases dopamine release, and blocks dopamine reuptake. Amantadine probably does not inhibit monoamine oxidase (MAO) enzyme. Moreover, the drug has many effects in the brain, including release of dopamine and norepinephrine from nerve endings. It appears to be an anticholinergic (specifically at alpha-7 nicotinic receptors) like the similar pharmaceutical memantine.In 2004, it was discovered that amantadine and memantine bind to and act as agonists of the σ1 receptor (Ki = 7.44 μM and 2.60 μM, respectively), and that activation of the σ1 receptor is involved in the dopaminergic effects of amantadine at therapeutically relevant concentrations. These findings may also extend to the other adamantanes such as adapromine, rimantadine, and bromantane, and could explain the psychostimulant-like effects of this family of compounds.