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

beta-Phenylethylamine (PE) hydrochloride injected intraperitoneally into rats was distributed evenly throughout 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 2H4]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 2H4]PE-to-PE ratios were decreased by pargyline pretreatment. Subsequent experiments showed that more alpha, alpha-2H2]PE than PE was present in whole brain, liver, and plasma of rats injected with an equimolar mixture of alpha, alpha-2H2]PE and PE. In contrast, beta, beta-2H2]PE was not enriched in comparison to PE under the same experimental conditions. We concluded that the basis for the enrichment of 2H4]PE and alpha, alpha-2H2]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.