The tryptamine-derived dopaminergic neurotoxin 1-trichloromethyl-l,2,3,4-tetrahydro--carboline ('TaClo'), which was found to occur in humans after intake of the hypnotic chloral hydrate, was also shown to strongly disturb serotonergic cells. Incubation experiments using the human serotonergic cell line JAR clearly revealed TaClo to significantly reduce serotonin (5-HT) uptake (IC50 = 59 M) and to induce a distinct loss of cellular viability at increasing TaClo concentrations. In contrast to well-known serotonergic neurotoxins such as amphetamines, however, TaClo toxicity is not mediated by the 5-HT transporter (5-HTT). In the presence of the specific 5-HTT inhibitor imipramine, the uptake of TaClo into JAR cells was not reduced, hinting at an exclusively passive penetration of this highly lipophilic -carboline through cell membranes. Similar toxic effects towards JAR cells were also observed for the 5-HT-related TaClo analog 6-hydroxy-l-trichloromethyl-l,2,3,4-tetrahydro--carboline ('6-OH-TaClo') (IC50 = 26 M). The dopamine-derived alkaloid-type heterocycle 6,7-dihydroxy-l-trichloromethyl-1,2,3,4-tetrahydroisoquinoline ('DaClo'), by contrast, was found to be less toxic, showing only a weak inhibitory activity (IC50 = 260 M) on 5-HT uptake. The pronounced toxicitiy of TaClo and 6-OH-TaClo against serotonergic cells became also evident from morphological findings: Dose-dependently, the survival of JAR cells was significantly impaired, while human dopaminergic IMR-32 cells were only moderately affected at similar toxin concentrations.