Amantadine

Not to be confused with Adamantine or Adamantane.

Amantadine
Clinical data
Trade namesGocovri, Symadine, Symmetrel, others
Other names1-Adamantylamine; 1-Adamantanamine; 1-Aminoadamantane; Midantane; Midantan
AHFS/Drugs.comMonograph
MedlinePlusa682064
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability86–90%[1]
Protein binding67%[1]
MetabolismMinimal (mostly to acetyl metabolites)[1]
Elimination half-life10–31 hours[1]
ExcretionUrine[1]
Identifiers
  • Adamantan-1-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.011.092 Edit this at Wikidata
Chemical and physical data
FormulaC10H17N
Molar mass151.253 g·mol−1
3D model (JSmol)
Melting point180 °C (356 °F) [6]
  • C1C2CC3CC1CC(C2)(C3)N
  • InChI=1S/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2 checkY
  • Key:DKNWSYNQZKUICI-UHFFFAOYSA-N checkY
  (verify)

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.[7][8] It is also used for a variety of other uses. The drug is taken by mouth.

Amantadine has a mild side effect profile. Common neurological side effects include drowsiness, lightheadedness, dizziness, and confusion.[9] Because of its effects on the central nervous system, it should be combined cautiously with additional central nervous system stimulants or anticholinergic drugs. Given that it is cleared by the kidneys, amantadine is contraindicated in persons with end stage kidney disease.[5] Due to its anticholinergic effects, it should be taken with caution by those with enlarged prostates or glaucoma.[10]

The pharmacology of amantadine is complex.[11][12] It acts as a sigma σ1 receptor agonist, nicotinic acetylcholine receptor negative allosteric modulator, dopaminergic agent, and weak NMDA receptor antagonist, among other actions.[11][12] The precise mechanism of action of its therapeutic effects in the treatment of central nervous system disorders is unclear.[11][12] 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).[13][14] Amantadine is an adamantane derivative and is related to memantine and rimantadine.[15]

Amantadine was first used for the treatment of influenza A.[11] After its antiviral properties were initially reported in 1963, amantadine received approval for prophylaxis against the influenza virus A in 1966.[11][16] In 1968, its antiparkinsonian effects were serendipitously discovered.[11] In 1973, the Food and Drug Administration (FDA) approved amantadine for use in the treatment of Parkinson's disease.[11] In 2020, the extended-release formulation was approved for use in the treatment of levodopa-induced dyskinesia.[11][17]

  1. ^ a b c d e f g "Symmetrel (amantadine hydrochloride)" (PDF). TGA eBusiness Services. Novartis Pharmaceuticals Australia Pty Limited. 29 June 2011. Retrieved 24 February 2014.
  2. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  3. ^ "Trilasym 50 mg/ 5 ml Oral Solution – Summary of Product Characteristics (SmPC)". (emc). 24 September 2019. Archived from the original on 26 March 2020. Retrieved 26 March 2020.
  4. ^ Cite error: The named reference Gocovri FDA label was invoked but never defined (see the help page).
  5. ^ a b "Gocovri- amantadine capsule, coated pellets". DailyMed. 26 December 2019. Retrieved 22 January 2020.
  6. ^ Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. p. 3.524. ISBN 9781498754293.
  7. ^ Cite error: The named reference CDC_2019 was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference WHO_2011 was invoked but never defined (see the help page).
  9. ^ Chang C, Ramphul K (2020). "Amantadine". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29763128. Retrieved 2 November 2020.
  10. ^ "Symmetrel (Amantadine Hydrochloride, USP) fact sheet" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 28 July 2019.
  11. ^ a b c d e f g h Cite error: The named reference DanyszDekundyScheschonka2021 was invoked but never defined (see the help page).
  12. ^ a b c Cite error: The named reference HuberDietrichEmrich1999 was invoked but never defined (see the help page).
  13. ^ James SH, Whitley RJ (2017). "Influenza Viruses". Infectious Diseases. Elsevier. pp. 1465–1471.e1. doi:10.1016/b978-0-7020-6285-8.00172-6. ISBN 978-0-7020-6285-8.
  14. ^ Balgi AD, Wang J, Cheng DY, Ma C, Pfeifer TA, Shimizu Y, et al. (1 February 2013). Bouvier NM (ed.). "Inhibitors of the influenza A virus M2 proton channel discovered using a high-throughput yeast growth restoration assay". PLOS ONE. 8 (2): e55271. Bibcode:2013PLoSO...855271B. doi:10.1371/journal.pone.0055271. PMC 3562233. PMID 23383318.
  15. ^ Ragshaniya A, Kumar V, Tittal RK, Lal K (March 2024). "Nascent pharmacological advancement in adamantane derivatives". Arch Pharm (Weinheim). 357 (3): e2300595. doi:10.1002/ardp.202300595. PMID 38128028.
  16. ^ Hubsher G, Haider M, Okun MS (April 2012). "Amantadine: the journey from fighting flu to treating Parkinson disease". Neurology. 78 (14): 1096–9. doi:10.1212/WNL.0b013e31824e8f0d. PMID 22474298. S2CID 21515610.
  17. ^ Hauser RA, Lytle J, Formella AE, Tanner CM (March 2022). "Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson's disease". npj Parkinson's Disease. 8 (1): 29. doi:10.1038/s41531-022-00291-1. PMC 8933492. PMID 35304480.