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Pharmacokinetics of Memantine-derivative MN-08 in Rats: A Preclinical Study

Chaoqiang Luo, Fangcheng Luo, Yewei Sun, Lipeng Xu, Pei Yu, Yuqiang Wang, Zaijun Zhang

Abstract


1-amino-3-methyl-5-nitrate methyl adamantane hydrochloride (MN-08), a novel nitrate derivative of memantine, was found to be a potent candidate compound for the treatment of Alzheimer disease in an animal model. A non-clinical pharmacokinetic study was carried out to investigate further uses of MN-08. According to the structure and properties of MN-08, a rapid and sensitive analytical method was established. This method was used to get some preliminary pharmacokinetic data of MN-08 in biological samples of rats. This method is believed to allow rapid access to further research of pharmacokinetics
and efficacy.

Keywords


pharmacokinetics, MN-08, HPLC, tissues distribution, plasma

Full Text:

References


Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994;330:613–622.

Bordji K, Becerril-Ortega J, Nicole O, Buisson A. Activation of extrasynaptic, but not synaptic, NMDA receptors modifies amyloid precursor protein expression pattern and increases amyloid-ss production. J Neurosci. 2010;30:15927–15942.

Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov. 2006;5:160–170.

Witt A, Macdonald N, Kirkpatrick P. Memantine hydrochloride. Nat Rev Drug Discov. 2004;3:109–110.

Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000;130:1007s–1015s.

Lipton SA, Nicotera P. Calcium, free radicals and excitotoxins in neuronal apoptosis. Cell Calcium. 1998;23:165–171.

Gilling KE, Jatzke C, Parsons CG. Agonist concentration dependency of blocking kinetics but not equilibrium block of N-methyl-D-aspartate receptors by memantine. Neuropharmacology.2007;53:415–420.

Lipton SA. Pathologically-activated therapeutics for neuroprotection:mechanism of NMDA receptor block by memantine and S-nitrosylation. Curr Drug Targets. 2007;8:621–632.

Akhtar MW, Sunico CR, Nakamura T, Lipton SA. Redox regulation of protein function via cysteine S-Nitrosylation and its relevance to neurodegenerative diseases. Int J Cell Biol. 2012;2012:463756.

Khan M, Sekhon B, Giri S, Jatana M, Gilg AG, Ayasolla K, et al. S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke. J Cereb Blood Flow Metab. 2005;25:177–192.

Willmot M, Gray L, Gibson C, Murphy S, Bath PM. A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow. Nitric Oxide. 2005;12:141–149.

Wang Y, Eu J, Washburn M, Gong T, Chen HS, James WL, et al. The pharmacology of aminoadamantane nitrates. Curr Alzheimer Res. 2006;3:201–204.

Freudenthaler S, Meineke I, Schreeb KH, Boakye E, Gundertremy U, Gleiter CH. Influence of urine pH and urinary flow on the renal excretion of memantine. Br J Clin Pharmacol. 1998;46:541–546.


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