ABSTRACT
In his monograph “The case of the frozen addicts,” William Langston reported the story of six patients, who, in 1982, in California, developed mysterious symptoms provoked by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that were reminiscent of Parkinson’s disease (PD). Since that time, MPTP has been recognized as a highly selective neurotoxin; in reality, this compound has a much longer history (1). Apparently, the synthesis of MPTP was first reported by Ziering and his colleagues in 1947 as part of a series of papers on meperidine derivatives (2), and, using these methods, it was shown that piperidols may be acylated with a propionic group to produce MPPP (1-methyl-4-phenyl-4-propionoxypiperidine), a compound 25 times more potent than morphine in the rat (2,3). Since then, MPTP has been used extensively as a synthetic intermediate in meperidine chemistry and has become commercially available (Aldrich Chemical Company, Milwaukee, Wisconsin) for this purpose long before it had been identified as a potent neurotoxin.
