The pharmacology of aminoadamantane nitrates.
Memantine, an aminodamantane, has recently been approved to treat moderate-to-severe Alzheimer's disease in the US after over 20 years on the market in Europe for treatment of Parkinson's disease. The unique properties of Memantine allow for its selective inhibition of abnormally active NMDA receptor channels while preserving normal glutamate activity and healthy neuronal function. Recently, it has been shown that compounds such as nitroglycerin, used for years for ischemic coronary disease, can also regulate the NMDA receptor channel. Novel compounds have been synthesized in an attempt to combine these activities, in an attempt to synergistically improve upon the activities of both nitrates and aminoadamantanes. We have subjected these compounds to several laboratory tests to compare their ability to affect the function of the NMDA receptor and to dilate blood vessels. These tests provide an initial indication of which of the compounds may have enhanced activity relative to memantine. The results also provide guidance for the synthesis of additional compounds that are likely to have the properties that are being sought.
Wang
Yuqiang
Y
NeuroMolecular Pharmaceuticals, Inc., 1050 Powell St., Emeryville, CA 94608, USA.
Eu
Jerry
J
Washburn
Mark
M
Gong
Tong
T
Chen
H-S Vincent
HS
James
W Larrick
WL
Lipton
Stuart A
SA
Stamler
Jonathan S
JS
Went
Gregory T
GT
Porter
Seth
S
D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D009566:Nitrates / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D011994:Recombinant Proteins; D015222:Sodium Channels / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D009566:Nitrates; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D015222:Sodium Channels; C513628:aminoadamantane nitrate; D000218:Adamantane