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A Novel and Neurotoxic Tetrahydroisoquinoline Derivative In Vivo: Formation of 1,3‐Dimethyl‐1,2,3,4‐Tetrahydroisoquinoline, a Condensation Product of Amphetamines, in Brains of Rats Under Chronic Ethanol Treatment
Author(s) -
Makino Yukiko,
Ohta Shigeru,
Tasaki Yoshikazu,
Tachikawa Osamu,
Kashiwasake Masaki,
Hirobe Masaaki
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb04585.x
Subject(s) - amphetamine , tetrahydroisoquinoline , ethanol , metabolite , chemistry , pharmacology , dopaminergic , serotonergic , in vivo , dopamine , medicine , biochemistry , serotonin , biology , receptor , microbiology and biotechnology
Repeated amphetamine administration to rats under chronic ethanol intoxication resulted in the formation of 1,3‐dimethyl‐1,2,3,4‐tetrahydroisoquinoline (1,3‐DiMeTIQ), a novel metabolite of amphetamines. 1,3‐DiMeTIQ was quantified with a sensitive, specific assay using gas chromatography‐mass spectrometry. It was not found in the brains of rats given repeated amphetamine administration but no ethanol. The chronic ethanol‐intoxicated rats subjected to repeated amphetamine administration exhibited behavioral abnormalities, such as repeated convulsions and curving of the back. 1,3‐DiMeTIQ contents were markedly higher in the brain or plasma of rats manifesting abnormal behavior in comparison with those in rats behaving normally. Thus, the 1,3‐DiMeTIQ content in the rat brain seems to have some relationship with behavioral abnormalities. This study also confirmed that 1,3‐DiMeTIQ can cross the blood‐brain barrier in the rat. Intraperitoneal 1,3‐DiMeTIQ injections to rats caused behavioral symptoms similar to those observed in rats with chronic ethanol intoxication and repeated amphetamine administration. The effect of toxic doses of 1,3‐DiMeTIQ on dopaminergic and serotonergic metabolism in the whole rat brain was also investigated.