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.
According to the CDC, 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 was discovered in 1963 and patented in 1965 in the USA by William W. Prichard in Du Pont & Co., Wilmington, Delaware (US patent on new chemical compound № 3352912, 1965 and on the first method of synthesis № 3592934, 1967). Prichard's methods of synthesis of rimantadine from the corresponding ketone oxime were based on its reduction with lithium aluminum hydride.
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 an 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, neither rimantadine nor amantadine are preferred agents for this therapy and are generally reserved for cases of the disease which are less responsive to front-line treatments.
^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.
^D. M. Zlydnikov, O. I. Kubar, T. P. Kovaleva, L. E. Kamforin. Study of Rimantadine in the USSR: A Review of the Literature. Clinical Infectious Diseases 3:408-421, p.408.
^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. doi:10.1073/pnas.0804958105. PMC2492755. PMID18669647.