'TaCIo', A CHLORAL-DERlVED MAMMALIAN ALKALOID WITH NEUROTOXIC PROPERTIES Gerhard Bringmann l , Ralph Bruckner l , Miriam Miinchbach l , Doris Feineis l , Ralf God l , Wolfgang Wesemann 2 , Christoph Grote 2 , Markus Herderich 3 , Stefanie Diem 3 , Klaus-Peter Lesch 4 , Rainald Mossner 4 and Alexander Storch 5 1 Institute of Organic Chemistry University of Wiirzburg 97074 Wiirzburg, Germany 2Institute of Physiological Chemistry University of Marburg 35033 Marburg, Germany 3Institute of Food Science University of Wiirzburg 97074 Wurzburg, Germany 4Department of Psychiatry University of Wiirzburg 97080 Wurzburg, Germany 5Department of Neurology University of UIm Medical School 89081 Ulm, Germany INTRODUCTION Since the discovery that the synthetic compound 1-methyl-4-phenyl-1,2,3,6-tetra- hydropyridine (MPTP, 5) induces parkinsonian-like symptoms in humans, monkeys, and mice, particular attention has been focused on the possible role of environmental toxic agents in causing damage to the central nervous system (Collins et al., 1986). We report on the highly halogenated heterocycle 1-trichloromethyl-1,2,3,4-tetra- hydro-{3-carboline ('TaClo', 4) (Bringmann et al., 1995, 1996, 1998), closely related structurally to MPTP (5). TaClo (4) readily originates in vitro under physiological conditions (pH= 7.4, T= 37°C) via a Pictet-Spengler type condensation from the biogenic amine tryptamine ('Ta', 1) and the synthetic aldehyde chloral ('Clo', 3) (see Figure 1). Its spontaneous formation in humans has thus to be taken into account Neurotoxic Factors ill Parkillsoll's Disease alld Related Disorders Edited by Storch and Collins. Kluwer Academic/Plenum Publishers. 2000 145