Deleterious Effects of Highly Halogenated ß-Carbolines on Dopaminergic Cells in Culture and on Mitochondrial Respiration

Abstract

Several psychotropically active ß-carbolines (e.g. harmane, norharman, harmin, and especially their N-methylated derivatives) have been described to exert neurotoxic effects to dopaminergic cells comparable to those of MPTP and its active metabolite MPP⁺. TaClo, a highly chlorinated tetrahydro-ß-carboline, readily originates under quasi-physiological conditions from the endogenously present tryptamine (“Ta”) and the non-natural aldehyde chloral (“Clo”). A spontaneous in vivo formation of TaClo may occur whenever chloral is incorporated, e.g. by uptake of the hypnotic drug chloral hydrate or by exposition to the industrial solvent trichloroethylene, which can be metabolized to chloral. Moreover, TaClo, as a lipophilic compound should have a higher ability to cross the blood-brain-barrier than e.g. halogen-free-ß-carbolines.