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

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Abstract
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.

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