Memantine and Adamantine KLVFF Conjugates: Synthesis, Ab interaction and Effects on Recognition Memory in Mice.

Adamantane derivatives, such as memantine (Mem) and amantadine (Ada), are clinically active drugs with distinct mechanisms of action and therapeutic applications.While Ada is primarily used as an antiviral and anti-Parkinson drug and is not reported to have significant pro-cognitive effects, Mem has been demonstrated to be effective in various clinical conditions characterized by cognitive deficits, including Alzheimer's disease (AD).In our mind, preserving Ab monomers from being recruited into oligomers may represent a viable therapeutic approach in AD.We designed and characterized two peptide conjugates of the KLVFF fragment bearing a memantinyl (Mem-Succ-KLVFF; Mem=3,5-dimethyladamantan-1amine,) or an amantadinyl (Ada-Succ-KLVFF; Ada=Adamantan-1-amine) moiety, linked to the KLVFF sequence through a succinyl spacer.Their ability to counteract in vitro Ab fibrillogensis and in vivo enhancement of memory performance was investigated REFERENCES