Tetrahydroisoquinoline (TIQ orTHIQ), also known asAMPH-CR, is anorganic compound with the chemical formula C9H11N. Classified as asecondary amine, it is derived fromisoquinoline by hydrogenation. It is a colorless viscous liquid that is miscible with most organic solvents. The tetrahydroisoquinoline skeleton is encountered in a number of bioactive compounds and drugs.[2][3]
As a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. It can be dehydrogenated to give isoquinoline and hydrogenated todecahydroisoquinoline. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the correspondingnitrone usinghydrogen peroxide, catalyzed byselenium dioxide.[6]
Tetrahydroisoquinoline derivatives may be formed in the body as metabolites of some drugs, and this was once thought to be involved in the development ofalcoholism.[7] This theory has now been discredited and is no longer generally accepted by the scientific community,[8] but endogenous production of neurotoxic tetrahydroisoquinoline derivatives such asnorsalsolinol continue to be investigated as possible causes for some conditions such asParkinson's disease.[9][10][11][12][13][14]
^Mitchenson, Andrew (2000). "Saturated nitrogen heterocycles".Journal of the Chemical Society, Perkin Transactions 1 (17):2862–2892.doi:10.1039/A908537H.
^abScott, Jack D.; Williams, Robert M. (2002). "Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics".Chemical Reviews.102 (5):1669–1730.doi:10.1021/cr010212u.PMID11996547.
^abcdGlennon RA, Young R, Rangisetty JB (May 2002). "Further characterization of the stimulus properties of 5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline".Pharmacol Biochem Behav.72 (1–2):379–387.doi:10.1016/s0091-3057(01)00768-7.PMID11900809.
^Murahashi, S. (1987). "Selenium dioxide catalyzed oxidation of secondary amines with hydrogen peroxide. Simple synthesis of nitrones from secondary amines".Tetrahedron Letters.28 (21):2383–2386.doi:10.1016/S0040-4039(00)96130-6.
^Blum, K.; Hamilton, M. G.; Hirst, M.; Wallace, J. E. (1978). "Putative role of isoquinoline alkaloids in alcoholism: a link to opiates".Alcoholism: Clinical and Experimental Research.2 (2):113–120.doi:10.1111/j.1530-0277.1978.tb04710.x.PMID350073.,Altshuler, H. L.; Shippenberg (1982). "Tetrahydroisoquinoline and opioid substrates of alcohol actions".Progress in Clinical and Biological Research.90:329–344.PMID7202207.,Myers, R. D. (1989). "Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms".Experientia.45 (5):436–443.doi:10.1007/BF01952025.PMID2656285.S2CID1513683.
^Myers, R. D. (1996). "Tetrahydroisoquinolines and alcoholism: where are we today?".Alcoholism: Clinical and Experimental Research.20 (3):498–500.doi:10.1111/j.1530-0277.1996.tb01081.x.PMID8727243.,Musshoff, F.; Daldrup, T.; Bonte, W.; Leitner, A.; Lesch, O. M. (1996). "Formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines in human urine".Journal of Chromatography B.683 (2):163–176.doi:10.1016/0378-4347(96)00106-5.PMID8891913.,Sällström Baum, S.; Hill, R.; Kiianmaa, K.; Rommelspacher, H. (1999). "Effect of ethanol on (R)- and (S)-salsolinol, salsoline, and THP in the nucleus accumbens of AA and ANA rats".Alcohol (Fayetteville, N.Y.).18 (2–3):165–169.doi:10.1016/S0741-8329(98)00080-9.PMID10456568.,Musshoff, F.; Lachenmeier, D. W.; Schmidt, P.; Dettmeyer, R.; Madea, B. (2005). "Systematic regional study of dopamine, norsalsolinol, and (R/S)-salsolinol levels in human brain areas of alcoholics".Alcoholism: Clinical and Experimental Research.29 (1):46–52.doi:10.1097/01.ALC.0000150011.81102.C2.PMID15654290.
^Kotake Y, Tasaki Y, Makino Y, Ohta S, Hirobe M (December 1995). "1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF".Journal of Neurochemistry.65 (6):2633–8.doi:10.1046/j.1471-4159.1995.65062633.x.PMID7595560.S2CID39449026.
^McNaught KS, Carrupt PA, Altomare C, Cellamare S, Carotti A, Testa B, Jenner P, Marsden CD (October 1998). "Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease".Biochemical Pharmacology.56 (8):921–33.doi:10.1016/S0006-2952(98)00142-7.PMID9776302.
^Lorenc-Koci E, Smiałowska M, Antkiewicz-Michaluk L, Gołembiowska K, Bajkowska M, Wolfarth S (2000). "Effect of acute and chronic administration of 1,2,3,4-tetrahydroisoquinoline on muscle tone, metabolism of dopamine in the striatum and tyrosine hydroxylase immunocytochemistry in the substantia nigra, in rats".Neuroscience.95 (4):1049–59.doi:10.1016/S0306-4522(99)00511-4.PMID10682712.S2CID13549697.
^Storch A, Ott S, Hwang YI, Ortmann R, Hein A, Frenzel S, Matsubara K, Ohta S, Wolf HU, Schwarz J (March 2002). "Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter".Biochemical Pharmacology.63 (5):909–20.doi:10.1016/S0006-2952(01)00922-4.PMID11911843.
^Lorenc-Koci E, Antkiewicz-Michaluk L, Kamińska A, Lenda T, Zieba B, Wierońska J, Smiałowska M, Schulze G, Rommelspacher H (October 2008). "The influence of acute and chronic administration of 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline on the function of the nigrostriatal dopaminergic system in rats".Neuroscience.156 (4):973–86.doi:10.1016/j.neuroscience.2008.08.050.PMID18809471.S2CID44658852.
^Schneider, C. S.; Weber, K. H.; Daniel, H.; Bechtel, W. D.; Boeke-Kuhn, K. (1984). "Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives".Journal of Medicinal Chemistry.27 (9):1150–1155.doi:10.1021/jm00375a011.PMID6471069.
^Gray, Allan P.; Shiley, Richard H. (1973). "Preparation and cardiovascular actions of a group of tetrahydroisoquinoline derivatives".Journal of Medicinal Chemistry.16 (7):859–861.doi:10.1021/jm00265a028.ISSN0022-2623.PMID4146907.
