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.
Riederer
Peter
P
Clinical Neurochemistry, Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, Würzburg, Germany. peter.riederer@mail.uni-wuerzburg.de
Foley
Paul
P
Bringmann
Gerhard
G
Feineis
Doris
D
Brückner
Ralph
R
Gerlach
Manfred
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002243:Carbolines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000493:pharmacokinetics / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution
D002243:Carbolines; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; C067372:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline; D012701:Serotonin