Trichloroharmanes as potential endogenously formed inducers of Morbus Parkinson: synthesis, analytics, and first in vivo-investigations.

The hypnotic chloral reacts chemically with tryptamine and tryptophan under physiological conditions to give novel trichloro-tetrahydroharmanes ("TTHs"). These are structurally similar to the classical neurotoxin MPTP. Moreover, the TTH-precursor chloral is also a metabolite of the frequently used solvent trichloroethylene (Tri). These properties and first hints at a neuropharmacological potential of this class of substances warrent investigations whether TTHs and other chloral-derived harmanes are formed endogenously and possibly have to do with the pathogenesis of Morbus Parkinson (MP). For an investigation of these problems, some fundamental methods and results had to be elaborated first: the synthesis of several representatives of this novel class of trichloroharmanes, sensitive analytical methods for the detection of these compounds even in biological matrices, and studies concerning their biological "fate".