Aminoadamantanes were first synthesized in the 1950’s and include FDA-approved amantadine, rimantadine and memantine. Amantadine HCl was introduced for prophylactic use against Influenza A in 1966 by Dupont Merck, and subsequently was approved for symptomatic treatment of Parkinson’s disease. Amantadine was not widely prescribed for either indication due to resistance concerns for flu and poor tolerability along with the arrival of new and more potent drugs for Parkinson’s disease. While amantadine’s mechanism of action in the treatment of influenza has been established, the mechanism for benefit in Parkinson’s (and other CNS conditions) has not been elucidated and may be associated with its ability to modulate multiple neurochemical pathways (e.g. glutamate, dopamine, serotonin). Memantine HCl was synthesized in 1963 by chemists at Eli Lilly, but was not approved for treatment of Alzheimer’s disease until 2002/2003 driven by the discovery of its mechanism by Dr. Stuart Lipton at Harvard,¹ Merz Pharmaceuticals in Germany,² and its development for the US market by Forest Laboratories.³ Memantine’s mechanism of action for the treatment of Alzheimer’s disease is thought to occur through modulations of glutamate signaling. The market for aminoadamantane-based drugs has flourished, with global sales of memantine for dementia exceeding $2 billion in 2011. Despite this, as a class of drugs, aminoadamantanes have not yet been fully explored by the pharmaceutical industry.

¹ Lipton, SA, 1991
² Bormann, et al, 1990
³ Tariot, et al, 2004