Memantine hydrochloride

Q8 The drugs currently licensed for Alzheimer s disease in Britain are cholinesterase inhibitors, with one exception-memantine hydrochloride. This agent... 

Memantine hydrochloride, an NMDA receptor antagonist, reduces glutamate transmission and has shown beneficial effects. 

Forest Laboratories, Inc. Namenda (memantine hydrochloride) package insert. New York, 2004. 

Mobius HJ, Stoffler A, Graham SM (2004) Memantine hydrochloride pharmacological and clinical profile. Drugs Today 40 685-695... 

Memantine hydrochloride is an A-methyl-D-aspartate (NMDA) receptor antagonist. It is postulated that memantine exerts its therapeutic effect as a low to moderate affinity, noncompetitive nervous system NMDA receptor antagonist by binding preferentially to the NMDA receptor-operated cation channels. 

The recommended initial dose of memantine hydrochloride for the treatment of moderate to severe dementia of Alzheimer s type is 5 mg orally once daily. The dose should be increased in 5 mg increments to 10 mg/day (given as 5 mg twice daily), 15 mg/day (given twice daily in separate doses of 5 mg and 10 mg), and 20 mg/day (given as 10 mgtwice daily). The minimum recommended interval between dose increases is 1 week. The recommended maintenance dose is 10 mg twice daily (20 mg/day). There is not an established dose for the treatment of chronic pain states, but case reports and medication trials have started at 5-10 mg BID and increases at 1 week intervals to 30 mg/day have been examined [3-5]. 

Yan, Y. Manufacture of memantine hydrochloride effervescent tablet for treating Alzheimer s disease. Faming ZhuanU Shenqing Gongkai Shuomingshu CN 1742711, 2006 Chem. Abstr. 2006, 144, 398290. 

In pharmacology, two adamantane derivatives. Amantadine (1-adamanta-neamine hydrochloride) and Rimantadine (a-methyl-1-adamantane methyla-mine hydrochloride) (see Fig. 24), have been well known because of their antiviral activity [129]. The main application of these drugs is prophylaxis (treatment to prevent the onset of a particular disease) and treatment of influenza-A viral infections. They are also used in the treatment of parkinsonism and inhibition of hepatitis-C virus. Memantine (1-amino-3,5-dimethyladaman-tane) (see Fig. 24) has been reported effective in slowing the progression of Alzheimer s disease [130]. 

Memantine. 3,S-Dimethyltricyclo[3.3.I.I3 ]decan-1-amine 3,S-dimethyl-l-adamantanamine 1 -amino-3,5-dimethyladamantane DMAA D 145. C.jH N mol wt 179.31. C 80.38%, H 11.81%, N 7.81%. Deriv of adaman-tine, q.v.. with anti-parkinson activity. Prepn of the hydrochloride K. Gerzon et al. J. Med. Chem. 6, 760 (1963) of the free base and hydrochloride J. Mills, E. Krumkalns, UJS. pat. 3,391,142 (1968 to Lilly). GC and mass spec studies of memantine metabolites W. Wesemann et al, Arznei-mittel-Forsch. 27, 1471 (1977), Effects in parkinsonian patients P. -A. Fischer er at., Ibid, 1487. Series of articles on distribution, effects on neurobiological processes, clinical studies in control of micturition and limb muscle mobility ibid. 32, 1236-1276 (1982). Clinical studies as antispasmod-ic agent H. Rohde, Fortschr. Med. 100, 2023 (1982). Pharmacodynamics and pharmacokinetics W. Wesemann et al, Arzneimittel-Forsch. 33, 1122 (1983). 

Troc protecting groups are easy to remove, which is an advantage associated with the use of 2,2,2-trichloroethyl-A/-tosyloxy-carbamate as a nitrene precursor cort5)ared to arylsulfamate, which require harsh reaction conditions to obtain the free amine. Both amantadine (R = H) and memantine (R = Me) hydrochloride were prepared in quantitative yields from the corresponding Troc-protected amino compounds (eq 5). ... 

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