Amantadine

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 because of widespread drug resistance. It is also used for a variety of other conditions. The drug is taken by mouth.

Amantadine has a mild side-effect profile. Common neurological side effects include drowsiness, lightheadedness, dizziness, and confusion. Because of its effects on the central nervous system (CNS), it should be combined cautiously with additional CNS stimulants or anticholinergic drugs. Given that it is cleared by the kidneys, amantadine is contraindicated in persons with end-stage kidney disease. Due to its anticholinergic effects, it should be taken with caution by those with enlarged prostates or glaucoma.

The pharmacology of amantadine is complex. It acts as a sigma σ₁ receptor agonist, nicotinic acetylcholine receptor negative allosteric modulator, dopaminergic agent, and weak NMDA receptor antagonist, among other actions. The precise mechanism of action of its therapeutic effects in the treatment of CNS disorders is unclear. The antiviral mechanism of action is inhibition of the influenza virus A M2 proton channel, which prevents endosomal escape (i.e., the release of viral genetic material into the host cytoplasm). Amantadine is an adamantane derivative and is related to memantine and rimantadine.

Amantadine was first used for the treatment of influenza A. After its antiviral properties were initially reported in 1963, amantadine received approval for prophylaxis against the influenza virus A in 1966. In 1968, its antiparkinsonian effects were serendipitously discovered. In 1973, the Food and Drug Administration (FDA) approved amantadine for use in the treatment of Parkinson's disease. In 2020, the extended-release formulation was approved for use in the treatment of levodopa-induced dyskinesia.

Amantadine was initially developed to prevent replication of the influenza A virus. Its main clinical use today is treatment of Parkinson's disease. Other uses include treatment of drug-induced extrapyramidal side effects, motor fluctuations during levodopa therapy in Parkinson's disease, traumatic brain injury, and autistic spectrum disorders.

Amantadine is used to treat Parkinson's disease-related dyskinesia and drug-induced parkinsonism syndromes. Amantadine may be used alone or in combination with another anti-Parkinson's or anticholinergic drug. The specific symptoms targeted by amantadine therapy are dyskinesia and rigidity. The extended release amantadine formulation is commonly used to treat dyskinesias in people receiving levodopa therapy for Parkinson's disease. A 2003 Cochrane review had concluded evidence was insufficient to prove the safety or efficacy of amantadine to treat dyskinesia.

In 2008, the World Health Organization (WHO) reported amantadine is not effective as a stand-alone parkinsonian therapy, but recommended it could be used in combination therapy with levodopa.

Amantadine is not recommended for treatment or prophylaxis of influenza A in the United States. Amantadine has no effect preventing or treating influenza B infections. The US Centers for Disease Control and Prevention (CDC) found 100% of seasonal H3N2 and 2009 pandemic flu samples were resistant to adamantanes (amantadine and rimantadine) during the 2008–2009 flu season.