Rimantadine (INN, sold under the trade name Flumadine) is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Both rimantadine and the similar drug amantadine are derivates of adamantane. Rimantadine was approved by the Food and Drug Administration (FDA) in 1994.
|Metabolism||Hepatic hydroxylation and glucuronidation|
|Elimination half-life||25.4 ± 6.3 hours|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||179.302 g/mol g·mol−1|
|3D model (JSmol)|
Rimantadine was approved for medical use in 1993. 100% of seasonal H3N2 and 2009 pandemic flu samples tested have shown resistance to rimantadine and it is no longer recommended to prescribe for treatment of the flu.
Rimantadine is believed to inhibit influenza's viral replication, possibly by preventing the uncoating of the virus's protective shells, which are the envelope and capsid. Genetic studies suggest that the virus M2 protein, an ion channel specified by virion M2 gene, plays an important role in the susceptibility of influenza A virus to inhibition by rimantadine. Resistance to rimantadine can occur as a result of amino acid substitutions at certain locations in the transmembrane region of M2. This prevents binding of the antiviral to the channel.
Rimantadine, like its antiviral cousin amantadine, possesses some NMDA antagonistic properties and is used as an antiparkinsonic drug (i.e., in the treatment of Parkinson's disease). However, in general, neither rimantadine nor amantadine is a preferred agent for this therapy and would be reserved for cases of the disease that are less responsive to front-line treatments.
Taking paracetamol (acetaminophen, Tylenol) or acetylsalicylic acid (aspirin) while taking rimantadine is known to reduce the body's uptake of rimantadine by approximately 12%. Cimetidine also affects the body's uptake of rimantadine.
Rimantadine can produce gastrointestinal and central nervous system adverse effects. Approximately 6% of patients (compared to 4% of patients taking a placebo) reported side-effects at a dosage of 200 mg/d. Common side effects include:
- upset stomach
- trouble sleeping
- difficulty concentrating
Rimantadine was discovered in 1963 and patented in 1965 in the US by William W. Prichard in Du Pont & Co., Wilmington, Delaware (patent on new chemical compound U.S. Patent 3,352,912, 1965 and on the first method of synthesis U.S. Patent 3,592,934, 1967). Prichard's methods of synthesis of rimantadine from the corresponding ketone oxime were based on its reduction with lithium aluminum hydride.
- Govorkova EA, Fang HB, Tan M, Webster RG (December 2004). "Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells". Antimicrobial Agents and Chemotherapy. 48 (12): 4855–63. doi:10.1128/AAC.48.12.4855-4863.2004. PMC 529183. PMID 15561867.
- Long, Sarah S.; Pickering, Larry K.; Prober, Charles G. (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN 978-1437727029.
- Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP)
- Jing X, Ma C, Ohigashi Y, et al. (August 2008). "Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel". Proc. Natl. Acad. Sci. U.S.A. 105 (31): 10967–72. Bibcode:2008PNAS..10510967J. doi:10.1073/pnas.0804958105. PMC 2492755. PMID 18669647.
- "fda.gov". Archived from the original on June 30, 2005. Retrieved 2008-11-05.
- "CDC - Influenza (Flu) | Antivirals: Side-Effects | REMOVED!". Retrieved 2008-11-05.
- US patent 3352912 to W. W. Prichard
- United States Patent № 4551552: Process for preparing rimantadine: Rimantadine and related compounds useful as antivirals were first described by Prichard in U.S. Pat. Nos. 3,352,912 and 3,592,934. Both patents describe the preparation of rimantadine from the corresponding ketone oxime by reduction with lithium aluminum hydride.
- United States Patent № 4551552: Process for preparing rimantadine
- Zlydnikov, D. M.; Kubar, O. I.; Kovaleva, T. P.; Kamforin, L. E. (1981). "Study of Rimantadine in the USSR: A Review of the Literature". Clinical Infectious Diseases. 3 (3): 408–421. doi:10.1093/clinids/3.3.408.