1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline

vanc 6 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline.svg skin-invert-image 200px None 6649-90-7 131384-80-0 119183 106473 TaClo; 1-Trichloromethyl-THβC; 1-TCMTC 1-(trichloromethyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole 12 11 3 2 C1CNC(C2=C1C3=CC=CC=C3N2)C(Cl)(Cl)Cl 1S/C12H11Cl3N2/c13-12(14,15)11-10-8(5-6-16-11)7-3-1-2-4-9(7)17-10/h1-4,11,16-17H,5-6H2 DPPAKKMPHBZNQA-UHFFFAOYSA-N 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (1-TCMTC), also known as tryptamine–chloral (TaClo), is a mammalian alkaloid and potent dopaminergic neurotoxin of the β-carboline family. Riederer P, Foley P, Bringmann G, Feineis D, Brückner R, Gerlach M May 2002 Biochemical and pharmacological characterization of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline: a biologically relevant neurotoxin? European Journal of Pharmacology 442 1–2 1–16 10.1016/s0014-2999(02)01308-0 12020676 Bringmann G, God R, Feineis D, Wesemann W, Riederer P, Rausch WD, Reichmann H, Sontag KH The TaClo concept: 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), a new toxin for dopaminergic neurons Journal of Neural Transmission. Supplementum 46 235–244 1995 8821060 Bringmann G, God R, Feineis D, Janetzky B, Reichmann H TaClo as a neurotoxic lead: improved synthesis, stereochemical analysis, and inhibition of the mitochondrial respiratory chain Journal of Neural Transmission. Supplementum 46 245–254 1995 8821061 It can form spontaneously in vivo as a condensation product of endogenous tryptamine (Ta) with chloral hydrate (Clo) or trichloroethylene. Janetzky B, God R, Bringmann G, Reichmann H 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline, a new inhibitor of complex I Journal of Neural Transmission. Supplementum 46 265–273 1995 8821063 Bringmann G, God R, Fähr S, Feineis D, Fornadi K, Fornadi F Identification of the dopaminergic neurotoxin 1-trichloromethyl-1,2, 3,4-tetrahydro-beta-carboline in human blood after intake of the hypnotic chloral hydrate Analytical Biochemistry 270 1 167–175 May 1999 10328779 10.1006/abio.1999.4088 Bringmann G, Feineis D, God R, Peters K, Peters EM, Scholz J, Riederer F, Moser A 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) and related derivatives: chemistry and biochemical effects on catecholamine biosynthesis Bioorganic & Medicinal Chemistry 10 7 2207–2214 July 2002 11983518 10.1016/s0968-0896(02)00060-3 Liu M, Shin EJ, Dang DK, Jin CH, Lee PH, Jeong JH, Park SJ, Kim YS, Xing B, Xin T, Bing G, Kim HC Trichloroethylene and Parkinson's Disease: Risk Assessment Molecular Neurobiology 55 7 6201–6214 July 2018 29270919 10.1007/s12035-017-0830-x The drug shows structural similarity to MPTP. Sontag KH, Heim C, Sontag TA, God R, Reichmann H, Wesemann W, Rausch WD, Riederer P, Bringmann G Long-term behavioural effects of TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) after subchronic treatment in rats Journal of Neural Transmission. Supplementum 46 283–289 1995 8821065 Heim C, Sontag KH The halogenated tetrahydro-beta-carboline "TaClo": a progressively-acting neurotoxin Journal of Neural Transmission. Supplementum Journal of Neural Transmission. Supplementa 50 107–111 1997 9120411 10.1007/978-3-7091-6842-4_11 978-3-211-82898-4 As with MPTP, it acts as an inhibitor of mitochondrial complex I, but shows greater potency in comparison. TaClo has been found to acutely elevate levels of serotonin and possibly dopamine in the brain in rodents, and elevated serotonin levels may be involved in its dopaminergic neurotoxicity. Gerlach M, Xiao AY, Heim C, Lan J, God R, Feineis D, Bringmann G, Riederer P, Sontag KH 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline increases extracellular serotonin and stimulates hydroxyl radical production in rats Neuroscience Letters 257 1 17–20 November 1998 9857955 10.1016/s0304-3940(98)00791-5 It exclusively enters serotonergic neurons via passive diffusion rather than by the serotonin transporter (SERT). Bringmann G, Brückner R, Mössner R, Feineis D, Heils A, Lesch KP Effect of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) on human serotonergic cells Neurochemical Research 25 6 837–843 June 2000 10944002 10.1023/a:1007521625088 TaClo produces long-lasting behavioral changes in rodents, such as parkinsonism, changes in locomotor activity, and altered sensitivity to dopaminergic drugs. Leuschner J, Beuscher N, Zimmermann T, Schürer M, Schulz HU, Jeromin J, Ritter H Untersuchungen zu Plasmaspiegeln des Neurotoxins 1-Trichlormethyl-1,2,3,4-tetrahydro-beta-carbolin (TaClo) beim Menschen nach oraler Verabreichung von Chloralhydrat The plasma level of the neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) in man after oral administration of chloral hydrate German Arzneimittelforschung 48 1 1–5 January 1998 9522023 While initially characterized as a dopaminergic neurotoxin, TaClo has since been reported to be non-selective, acting as a general strong cytotoxin and without specificity for dopaminergic neurons nor for neurons generally. Storch A, Hwang YI, Bringmann G, Feineis D, Ott S, Brückner R, Schwarz J Cytotoxicity of chloral-derived beta-carbolines is not specific towards neuronal nor dopaminergic cells Journal of Neural Transmission 113 12 1895–1901 December 2006 16868795 10.1007/s00702-006-0495-5 The chemical synthesis of TaClo has been described. The N-methyl derivative of TaClo, N-methyl-TaClo, is a more potent dopaminergic neurotoxin than TaClo. Grote C, Clement HW, Wesemann W, Bringmann G, Feineis D, Riederer P, Sontag KH Biochemical lesions of the nigrostriatal system by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) and derivatives Journal of Neural Transmission. Supplementum 46 275–281 1995 8821064 Another analogue, TaBro, is also more potent. Other analogues have been described as well. Bringmann G, Münchbach M, Feineis D, Faulhaber K, Ihmels H May 2001 Studies on single-strand scissions to cell-free plasmid DNA by the dopaminergic neurotoxin 'TaClo' (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) Neuroscience Letters 304 1–2 41–44 10.1016/s0304-3940(01)01731-1 11335050 TaClo was first described in the scientific literature in 1990. Bringmann G, Hille A Endogenous alkaloids in man, VII: 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline--a potential chloral-derived indol alkaloid in man Archiv der Pharmazie 323 9 567–569 September 1990 2288478 10.1002/ardp.19903230903 It was subsequently described as a neurotoxin in 1995. The compound may be an endogenous or environmental neurotoxin and might be involved in the development of Parkinson's disease in some people. Kochen W, Kohlmüller D, De Biasi P, Ramsay R The endogeneous formation of highly chlorinated tetrahydro-beta-carbolines as a possible causative mechanism in idiopathic Parkinson's disease The Endogeneous Formation of Highly Chlorinated Tetrahydro-ß-Carbolines as a Possible Causative Mechanism in Idiopathic Parkinson's Disease Advances in Experimental Medicine and Biology 527 253–263 2003 15206739 10.1007/978-1-4615-0135-0_29 978-1-4613-4939-6 See also Substituted β-carboline Monoamine neurotoxin References Category:Human drug metabolites Category:Monoaminergic neurotoxins Category:Trichloromethyl compounds Category:Tryptolines Category:Beta-Carbolines