Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended due to widespread drug resistance. It acts as a nicotinic antagonist, dopamine agonist, and noncompetitive NMDA antagonist. The antiviral mechanism of action is antagonism of the influenzavirus A M2 proton channel, which prevents endosomal escape (i.e. the release of viral genetic material into the host cytoplasm). Amantadine was first used for the treatment of influenza A. After antiviral properties were initially reported in 1963, amantadine received approval for prophylaxis against the influenza virus A in 1976. In 1973, the Food and Drug Administration (FDA) approved amantadine for use in the treatment of Parkinson's disease. In 2017, the extended release formulation was approved for use in the treatment of levodopa-induced dyskinesia. Amantadine has a mild side effect profile. Common neurological side effects include drowsiness, light headedness, dizziness, and confusion. Due to its effects on the central nervous system, it should not be combined with additional CNS stimulants or anticholinergic 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. 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 Parkinson's 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. There has