The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5^′Untranslated-Region-Directed Translation Blockers of the Parkinson’s Alpha Synuclein Expression

Figure 5

Metabolic analogs of posiphen and their respective anticholinesterase activities [60]. Posiphen is devoid of anticholinesterase activity. However, its phase 1 metabolites, N8 demethylated, N1 demethylated, and di-demethylated N1, N8-bisnorposiphen showed ex vivo AChE and BChE inhibitory activity of clinical relevance [61, 62]. The compound N8-bisnorposiphen demonstrated no AChE activity. This activity has proven to be dose limiting in human safety studies.