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Effects of Deuterium Substitution on the Catabolism of β‐Phenylethylamine: An In Vivo Study

Journal of Neurochemistry, ISSN: 1471-4159, Vol: 46, Issue: 2, Page: 399-404
1986
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Abstract: β‐Phenylethylamine (PE) hydrochloride injected intraperitoneally into rats was distributed evenly throughout the various regions of rat brain. Similarly, when a mixture of PE and α, α, β, β‐deuterated PE ([H]PE) was injected, no regional differences were observed in the ratios of the amounts of [H]PE and PE present; however, significantly more [H]PE than PE was present, although a 1:1 mixture had been administered. Further experiments in which the amounts of [H]PE and PE in whole rat brain, liver, and plasma were quantified confirmed this finding. The maximum [H]PE‐to‐PE ratios observed were 67 in whole brain 1 h after injection and 8 in liver and in plasma 45 min after injection. The whole brain [H]PE‐to‐PE ratios were decreased by pargyline pretreatment. Subsequent experiments showed that more α, α‐[H]PE than PE was present in whole brain, liver, and plasma of rats injected with an equimolar mixture of α, α‐[H]PE and PE. In contrast, β, β‐[H]PE was not enriched in comparison to PE under the same experimental conditions. We concluded that the basis for the enrichment of [H]PE and α, α‐[H]PE compared to PE was due to protection of the deuterated analogs from the actions of monoamine oxidase and perhaps aldehyde dehydrogenase; this protection led to pronounced deuterium substitution effects in vivo especially in the brain. Copyright © 1986, Wiley Blackwell. All rights reserved

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