Adamas’ lead programs are based on aminoadamantanes, an underutilized but clinically validated class of
compounds. Aminoadamantanes were first synthesized in the 1950’s and include the FDA-approved products amantadine
and memantine. Aminoadamantanes as a class have the ability to stimulate multiple neurotransmitter systems,
and may have broader therapeutic utility than previously realized.
Amantadine 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 Parkinson’s after the launch of levodopa and dopamine agonists, in part due to tolerability
issues that arise at doses above 200 mg/day when amantadine shows a benefit. Amantadine’s mechanism of
action in Parkinson's (and other CNS conditions) is still being elucidated and may be associated with its
ability to modulate multiple neurochemical pathways (e.g. glutamate, dopamine).
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 in part by the discovery of its mechanism by Dr. Stuart
Lipton at Harvard, Merz Pharmaceuticals in Germany, and its development for the US market by Forest
Laboratories. 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, aminoadamantanes as a class have not yet been fully explored
by the pharmaceutical industry.