Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Memantine (Namenda) is prescribed as a treatment for moderate to severe Alzheimer's Disease. Memantine functions by blocking the NMDA receptor, but the key binding interactions between drug and receptor are not fully elucidated. To determine key binding interactions of memantine, we made side-by-side comparisons of IC(50) for memantine and amantadine, a structurally related drug, in the GluN1/GluN2B NMDA receptor. We identified hydrophobic binding pockets for the two methyl groups on memantine formed by the residues A645 and A644 on the third transmembrane helices of GluN1 and GluN2B, respectively. Moreover, we found that while adding two methyl groups to amantadine to produce memantine greatly improves affinity, adding a third methyl group to produce the symmetrical trimethylamantadine diminished affinity. Our results provide a better understanding of chemical-scale interactions between memantine and the NMDA channel, which will potentially benefit the development of new drugs for neurodegenerative diseases involving NMDA receptors.
ACS Chem Neurosci 2013 Feb 20
PMID:Key binding interactions for memantine in the NMDA receptor. 2342 76

Memantine hydrochloride is a medicine used for the treatment of Alzheimer's disease. A number of methods for the preparation of memantine hydrochloride have been reported. These procedures started from 1,3-dimethyl-adamantane by as many as using three or four reaction steps to produce memantine hydrochloride with overall yields ranging from 54 to 77%. In this article, a simple, concise two-step synthesis of memantine hydrochloride from 1,3-dimethyl-adamantane via N-formamido-3,5-dimethyl-adamantane with an improved overall yield of 83% was developed. In step 1, 3,5-dimethyl-adamantane was reacted with formamide and nitric acid to afford 1-formamido-3,5-dimethyl-adamantane in 98% yield, followed by hydrolysis of 1-formamido-3,5-dimethyl-adamantane with aq hydrochloride to give memantine hydrochloride in 85% yield. The procedure can be easily deployed at an industrial scale.
ACS Omega 2020 Jul 07
PMID:Simple Two-step Procedure for the Synthesis of Memantine Hydrochloride from 1,3-Dimethyl-adamantane. 3307 57