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

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Abstract
.beta.-Phenethylamine (PE) hydrochloride injected intraperitoneally into rats was distributed evenly througout the various regions of rat brain. Similarly, when a mixture of PE and .alpha., .alpha., .beta., .beta.-deuterated PE ([2H4]PE) was injected, no regional differences were observed in the ratios of the amounts of [2H4]PE and PE present; however, significantly more [2H4]PE than PE was present; although a 1:1 mixture had been administered. Further experiments in which the amounts of [2H]PE and PE in whole rat brain, liver, and plasma were quantified confirmed this finding. The maximum [2H4]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 [2H]PE-to-PE ratios were decreased by pargyline pretreatment. Subsequent experiments showed that more .alpha., .alpha.-[2H]PE than PE was present in whole brain, liver, and plasma of rats injected with an equimolar mixture of .alpha., .alpha.-[2H]PE and PE. In contrast, .beta., .beta.-[2H]PE was not enriched in comparison to PE under the same experimental conditions. We concluded that the basif for the enrichment of [2H]PE and .alpha., .alpha.-[2H]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 expecially in the brain.