Biochemical and pharmacological characterization of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline: a biologically relevant neurotoxin?

Acute and long-term effects of exposure to reactive compounds as the result of environmental pollution, workplace conditions or dietary intake are suspected to be involved in the etiology of a variety of disorders, including neurodegenerative disorders such as Parkinson's disease. The recognition in 1970s that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxic by-product of illicit meperidine synthesis, elicits parkinsonian symptoms in primates, including man, prompted the search for naturally occurring analogs which might be involved in human disease. It has been suggested that one candidate, 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), a potent dopaminergic neurotoxin, might be formed endogenously in humans following the administration of the hypnotic chloral hydrate or after the exposure to the industrial solvent trichloroethylene. Such spontaneous formation has, indeed, been recently reported. The biochemical and pharmacological characteristics of TaClo and related compounds are thus reviewed here, and their potential significance for human neurodegenerative disease discussed.