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

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.

Super Acid-Induced Pummerer-Type Cyclization Reaction: Improvement in the Synthesis of Chiral 1,3-Dimethyl-1,2,3,4-tetrahydroisoquinolines

“…The reaction using 21 molar equivalent of TFSA also enhanced the Friedel-Crafts reaction to yield 7bB in an exclusive manner (91%) ( Table 1, entry 9). The sulfoxide (ent-4b) in the reactions gave similar results to those of the enantiomer (4b), thus producing the corresponding 1,3-DiMeTIQ (ent-6b) and , as shown in Table 1 (entries 10,11,12).…”

The role of nitric oxide on bone metabolism in ovariectomized rats following chronic ethanol intake

“…This gradual increase method is very safe for inducing chronic alcoholism in rats (Makino et al, 1990;Elmas et al, 2001).…”

Update on epidemiological aspects of progressive supranuclear palsy

“…Biochemical analysis of the central nervous system of 3 of those atypical parkinsonian patients with a PSP phenotype who recently died showed a 4‐R tauopathy 42. There is evidence that TIQs are potentially neurotoxic 43–46. TIQs have been found in parkinsonian brains47 and levels of 1‐benzyl‐TIQs are elevated in the cerebrospinal fluid of PD patients 48.…”