Osamu Tachikawa

Presence of tetrahydroisoquinoline and 1-methyl-tetrahydro-isoquinoline in foods: Compounds related to Parkinson's disease

This is the first report confirming the presence of 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline(1MeTIQ) in a number of foods with a high 2-phenylethylamine content. These compounds were determined by gas chromatography-mass spectrometry. This study also confirmed that 1MeTIQ and TIQ can cross the blood-brain barrier in rat. Thus, these compounds, suspected to have relation to parkinsons disease, may accumulate in the brain from food sources.

Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer

4-Hydroxytetrahydroisoquinoline (4OH-TIQ) was detected as a metabolite of a possible parkinsonism-inducing substance, tetrahydroisoquinoline (TIQ), in rat liver microsomes and rat urine. Urinary excretion of 4OH-TIQ was significantly reduced in female DA rat, an animal model of a poor debrisoquine metabolizer. The female DA rat also showed significantly higher brain accumulation of TIQ. These results suggest that the metabolic detoxication process is depressed and TIQ accumulation in the brain is enhanced in a poor debrisoquine metabolizer, which may be one possible explanation for poor debrisoquine metabolizers being susceptible to Parkinsons disease.

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.

Dmitryivanovite: A new high-pressure calcium aluminum oxide from the Northwest Africa 470 CH3 chondrite characterized using electron backscatter diffraction analysis

Abstract Dmitryivanovite (CaAl2O4) is a newly described, calcium aluminum oxide from the Northwest Africa 470 (NWA470) CH3 chondrite (Ivanova et al. 2002). NWA470 contains abundant small Ca,Alrich inclusions (CAIs), and dmitryivanovite, whose composition is close to stoichiometric CaAl2O4 [Ca1.000(Al1.993Si0.003Ti0.002)1.998O4], was found in one of these CAIs. It occurs as ~10 μm subhedral grains intergrown with grossite (CaAl4O7), perovskite, and melilite. Electron backscatter diffraction (EBSD) analysis revealed that dmitryivanovite is a high-pressure polymorph of CaAl2O4 (a = 7.95, b = 8.62, c = 10.25 Å, β = 93.1°, space group P21/c, and Z = 12). Dmitryivanovite is the third phase to be described from nature in the binary system of CaO-Al2O3, the other two being hibonite (CaAl12O19) and grossite (CaAl4O7)-all are found in CAIs. The presence of CaAl2O4 in NWA470 suggests a local elevated dust/gas ratio in the solar nebula. The phase diagram of CaAl2O4 shows that ~2 GPa is required to stabilize the high-pressure CaAl2O4 polymorph at 1327 °C, above which CaAl2O4 condenses from the solar nebula. Because it is unlikely that the solar nebula ever had such a high total gas pressure, it appears more probable that condensation of the low-pressure polymorph occurred in the solar nebula with an enhanced dust-to-gas ratio and that subsequently the high-pressure polymorph was produced by shock metamorphism, most likely after the CaAl2O4-bearing CAI was incorporated into the NWA470 parent asteroid.

Andreyivanovite: A second new phosphide from the Kaidun meteorite

Abstract Andreyivanovite (ideally FeCrP) is another new phosphide species from the Kaidun meteorite, which fell in South Yemen in 1980. Kaidun is a unique breccia containing an unprecedented variety of fragments of different chondritic as well as achondritic lithologies. Andreyivanovite was found as individual grains and linear arrays of grains with a maximum dimension of 8 μm within two masses of Fe-rich serpentine. In one sample, it is associated with Fe-Ni-Cr sulfides and florenskyite (FeTiP). Andreyivanovite is creamy white in reflected light, and its luster is metallic. The average of nine electron microprobe analyses yielded the formula Fe(Cr0.587Fe0.150V0.109Ti0.081Ni0.060Co0.002)P. Examination of single grains of andreyivanovite using Laue patterns collected by in situ synchrotron X-ray diffraction (XRD), and by electron-backscatter diffraction revealed it to be isostructural with florenskyite; we were unable to find single crystals of sufficient quality to perform a complete structure analysis. Andreyivanovite crystallizes in the space group Pnma, and has the anti-PbCl2 structure. Previously determined cell constants of synthetic material [a = 5.833(1), b = 3.569(1), and c = 6.658(1) Å] were consistent with our XRD work. We used the XPOW program to calculate a powder-XRD pattern; the 5 most intense reflections are d = 2.247 (I = 100), 2.074 (81), 2.258 (46), 1.785 (43), and 1.885 Å (34). Andreyivanovite is the second new phosphide to be described from the Kaidun meteorite. Andreyivanovite could have formed as a result of cooling and crystallization of a melted precursor consisting mainly of Fe-Ni metal enriched in P, Ti, and Cr. Serpentine associated with andreyivanovite would then have formed during aqueous alteration on the parent asteroid. It is also possible that the andreyivanovite could have formed during aqueous alteration; however, artificial FeTiP has been synthesized only during melting experiments, at low oxygen fugacity, and there is no evidence that a hydrothermal genesis is reasonable.

Organometallic compounds : XXXII. Syntheses of 1,3-disubstituted ferrocenes and intermolecular (1,3)ferrocenophanes

Abstract 1,3-Diformylferrocene (VI) and its derivatives, which are precursors for the syntheses of (1,3)ferrocenophanes, have been synthesized. [2.2.2](1,3)Ferrocenophane (X) and dithia[3.3](1,3)ferrocenophanes (XI and XII) are the first examples of intermolecular (1,3)ferrocenophanes and have been synthesized by coupling of 1,3-disubstituted ferrocenes.

Formation of a Novel and Neurotoxic Tetrahydroisoquinoline Derivative, 1,3-Dimethyltetrahydroisoquinoline (1, 3DiMeTIQ), a Condensation Product of Amphetamines and Acetaldehyde in Vivo

d-Amphetamine and alcohol are generally thought to be mutually antagonistic with respect to their pharmacological action. However the toxic effect of d-amphetamines is not appreciably reduced by the concomitant administration of alcohol.1 It is reported that the combined abuse of methamphetamine and alcohol causes a significant increase in psychosomatic disorders than the abuse of methamphetamine only.2 We hypothesized that a novel metabolite of amphetamines may be involved in such disorders and proposed that 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) are formed by ring cyclization of endogenous phenylethylamine.3–5 In the present study, we examined the possibility that 1,3DiMeTIQ could be formed from exogenous amphetamines, an analog of phenylethylamine, by cyclization with acetaldehyde, a metabolite of ethanol (Fig. 1).

Relationship between TIQs and Parkinson’s disease

1,2,3,4-Tetrahydroisoquinoline (TIQ) has been assumed to be one of the endogenous substances inducing Parkinson’s disease because of its structural similarity to 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Importance of 1-Methyltetrahydroisoquinoline (1MeTIQ) in Parkinson’s Disease

The existence of endogenous 1-methyl-l,2,3,4-tetrahydro-isoquinoline (1MeTIQ) accompanied with 1,2,3,4-tetrahydro-isoquinoline (TIQ) in the rat brain has been confirmed in our previous research.1 The possibility of TIQ and 1MeTIQ intake from some foods was also pointed out.2 Recently, the neurotoxic properties of TIQ have been discussed, especially with regard to Parkinson’s disease.3–7 In spite of structural similarity to TIQ, there has been no study for the role of 1MeTIQ, the structure of which is shown in Fig. 1, in Parkinson’s disease, except for our work that confirmed a decrease in 1MeTIQ content in parkinsonian brain.8