Potentiation of the biochemical effects of beta-phenylethylhydrazine by deuterium substitution.
The concentrations of dopamine (DA), m-tyramine (mTA), p-tyramine (pTA) and serotonin (5-HT) in the striata of rats 18 hr after the administration of three different doses (5, 50, or 100 mg/kg) of beta-phenylethylhydrazine (phenelzine, PEH) were measured. These concentrations were compared to those following the administration of the same doses of 1,1,2,2-tetradeutero-PEH (d4PEH). In general, PEH and d4PEH caused dose-dependent increases in the levels of mTA, pTA and 5-HT. The lowest dose of d4PEH caused greater increases than PEH in the levels of all four monoamines. The concentration of 5-HT was increased more by d4PEH than PEH at all three doses. The inhibition of mitochondrial MAO obtained from rat striatum by PEH or d4PEH in vitro revealed no differences. However, the inhibition of striatal MAO obtained from rats injected with d4PEH was found to be greater than that from rats injected with PEH. It was concluded that deuteration of PEH potentiates its ability to inhibit MAO following its administration to the rat by slowing its degradation in vivo.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003903:Deuterium; D004298:Dopamine / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D010624:Phenelzine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014439:Tyramine / Q000378:metabolism*
D012701:Serotonin; D003903:Deuterium; D008995:Monoamine Oxidase; D010624:Phenelzine; D004298:Dopamine; D014439:Tyramine