Phenothiazine: the seven lives of pharmacology's first lead structure

Abstract

Rooted in the early days of organic dye chemistry, the phenothiazine structure and its derivatives have since held a prominent place in pharmacology and biomedicine. Initially used for histochemical stains of plasmodia by Paul Ehrlich, anthelmintic and antibiotic properties of phenothiazines were globally exploited in the 1930s and 1940s. Clinical use of N-substituted phenothiazines as antihistaminics (1940s), sedatives and antipsychotics (1950s) followed and continues to this day. Recently, interest in these structures has re-emerged for a variety of fascinating features in relation to neurodegenerative disease, spearheaded by the unique redox chemistry of phenothiazine--arguably the most potent chain-breaking antioxidant ever identified.