Amantadine, structure

Figure 24. Chemical structures of (a) Amantadine, (b) Rimantadine, and (c) Memantine.

Luginger E, Wenning GK, BOsch S, Poewe W (2000) Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson s disease. Mov Disord 15 873-878 Ly CD, Roche KW, Lee HK, Wenthold RJ (2002) Identification of rat EMAP, a delta-glutamate receptor binding protein. Biochem Biophys Res Commun 291 85-90 Madden DR (2002) The structure and function of glutamate receptor ion channels. Nat Rev Neurosci 3 91-101... 

Aldose reductase inhibitors Structure-activity relationships and therapeutic potential, 18, 139 Alzheimer s Disease A pharmacological challenge, 25, 203 Amantadine, 8, 11... 

Fig. 10.3 Chemical structures of low affinity NMDA antagonists used for the treatment of AD, AD, AIDS dementia, and migrane. Memantine (a) Amantadine (b) (R,S)-N-2-(4-(3-thienyl)phenyl)-2-propanesulfonamide (LY392098) (c) and (R)-4 -[l-fluoro-l-methyl-2-(propane-2-sulphonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide (LY503430) (d)...

Figure 13.8. Chemical structure of amantadine and of centrally acting anticholinergic agents used in the treatment of Parkinsonism. The antiviral compound amantadine is a dopamine-releasing agent with some anticholinergic activity.

Hu J, Asbury T, Achuthan S, Li C, Bertram R, Quine JR, Fu R, Cross TA. Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from Influenza A virus. Biophys. J. 2007 92 4335-4343. 

Amantadine is a symmetrical CIO tricyclic amine with an unusual structure (1-adamantanamine hydrochloride). It interferes with virus uncoating (1) by blocking the M2 ion channel, which is needed to affect a pH change that helps to initiate the uncoating process. Most consistent antiviral activity has been observed against influenza A virus, but amantadine has httle or no activity against influenza B virus (2). However, influenza A virus can become rapidly resistant to amantadine in vitro (3). Amantadine also promotes the release of dopamine from nerve endings, but may also delay its reuptake into synaptic vesicles. 

Rimatadine is structurally similar to amantadine, and has a similar spectrum of antiviral activity. No nephrotoxicity has been described with rimatadine. 

Amantadine is a primary amine, with a pKa of 10.8, and most of the drug is in the protonated form at physiologic pH. Nevertheless, the drug may enter the brain because of its cage-like structure that not only increases its lipophilicity but also precludes its catabolism by oxidative enzymes metabolism studies have shown that amantadine is excreted in the urine unchanged. 

Rimantadine hydrochloride (a-methyl-1-adamantanemethylamine hydrochloride) is a synthetic adamatane derivative that is structurally and pharmacologically related to amantadine (21,22). It appears to be more effective than amantadine hydrochloride against influenza A, with fewer CNS side effects. Rimantadine hydrochloride is thought to interfere with virus uncoating by inhibiting the release of specific proteins. It may act by inhibiting RT or the synthesis of virus-specific RNA, but it does not inhibit virus adsorption or penetration. It appears to produce a virustatic effect early in the virus replication. It is used widely in Russia and Europe. 

Cady SD, Schmidt-Rohr K, Wang J, Soto CS, Degrado WF, Hong M (2010) Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers. Nature 463 689-692... 

Fig. 9.8 Chemical structures of memantine and its derivatives. Amantadine (1-aminoadamantane) (a) memantine (l-amino-3,5-dimethyladamantane) (b) NitroMemantine (c) and 1-amino-3,...

Amantadine interacts with catecholamines in the central nervous system and in the periphery. This might be predicted from its prinmry amine structure. How can these interactions contribute to its effect in parkinsonism Table 1 lists five mechanisms by which amantadine and other drugs could counteract the deficit of extrapyramidal inhibition which is responsible for symptoms of parkinsonism. 

Manufacturer HOSPIRA, Inc., Chicago, IL Chemical Structure see Figure 79.1 Chemical Name magnesium sulfate Chemical Formula MgSO molecular wt 120.3 Generic Name amantadine, see Figure 79.2 Trade/Proprietary Name Symmetrel Manufacturer Endo Pharmaceuticals, Inc., Chadds Ford, PA... 

Structure-activity relationships within the amantadine series have been discussed. ... 

Adamantane has a carbon skeleton also found as part of the structure of diamond. Amantadine, which has an amino group bonded to the adamantane structure, is useful in the prevention of infection by influenza A viruses. What are the molecular formulas of adamantane and amantadine How many rings are in each structure ... 

A recent study of a construct containing the transmembrane helix and the amphi-pathic helix of the S3 IN mutant [167], which was reversely isotope labeled for four hydrophobic residues, facilitated sequential resonance assignments for 23 residues. All secondary chemical shifts were found to be characteristic for a-helical secondary structure. Peak doubling of most resonances as well as cross peaks between resonance pairs in PDSD spectra indicates that the tetramer is a dimer of asymmetric dimers instead of a symmetric homotetramer. Upon addition of amantadine, no significant shift changes were observed, which is in agreement with the drugs resistance of this mutant. 

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