Methamphetamine Enantiomers: From Chemical Synthesis to Biological Fate
Larissa Pires do Espírito Santo, Renato Lúcio de Carvalho, Juliana Almeida Sad, Pedro Henrique Costa dos Santos, Rhaiza Silva Domingues, Gabriele de Azevedo Cardoso, Karine Braga Enes, Gisele Assis Castro Goulart, Maila de Castro Lourenço das Neves, Ângelo de FátimaABSTRACT
Methamphetamine, an amphetamine‐type stimulant, is a potent and psychoactive compound distinguished by the presence of a single stereogenic center in its structure. Consequently, it exists as two enantiomers: ( S )‐(+)‐methamphetamine [( S )‐(+)‐MA ( 1 )] and ( R )‐(−)‐methamphetamine [( R )‐(−)‐MA ( 2 )]. The chirality of these molecules confers distinct biological and pharmacological properties, with notable differences between the two forms. These enantioselective variations extend beyond their mechanisms of action, encompassing differences in the central nervous system interactions, metabolism, excretion, and other physiological processes. Understanding these disparities is crucial for elucidating the pharmacological and potential therapeutic profiles of each enantiomer. Achieving such insight requires examination of the enantioselective synthetic routes through which the desired chirality can be either inherited or constructed. This review integrates chemical and biological perspectives to provide a comprehensive overview of both methamphetamine enantiomers, thereby bridging the gap between laboratory synthesis and biological behavior in these two chemically fascinating yet dangerous molecules.