Synthesis and biological evaluation of memantine nitrates as a potential treatment for neurodegenerative diseases.

A series of memantine nitrate derivatives, as dual functional compounds with neuroprotective and vasodilatory activity for neurodegenerative diseases, was designed and synthesized. These compounds combined the memantine skeleton and a nitrate moiety, and thus inhibited the -methyl-d-aspartic acid receptor and released NO in the central nervous system. The biological evaluation results revealed that the new memantine nitrates were effective in protecting neurons against glutamate-induced injury . Moreover, memantine nitrates dilated aortic rings against phenylephrine-induced contraction. The structure-activity relationships of neuroprotection and vasodilation were both analyzed. In further studies, compound significantly protected cortical neurons by inhibiting Ca influx, reducing free radical production and maintaining the mitochondrial membrane potential. Further research on is warranted.