Effect of chronic deuterated and non-deuterated phenelzine on rat brain monoamines and monoamine oxidase.
The effects of phenelzine and 1,1-dideuterophenelzine (0.5 or 2.5 mg/kg/day) administered s.c. via miniosmotic pumps for 13 days were compared. Striatal levels of p-tryrosine and tryptophan were unaffected by either treatment. The concentrations of DOPAC, HVA and 5-HIAA were dose-dependently decreased by phenelzine and deuterated phenelzine; furthermore, the deuterated compound decreased the amounts of these acids more than the same dose of phenelzine. Dopamine levels were increased by a rather small amount by all drug treatments; no effects of drug dose or drug type (deuterated or nondeuterated) were observed. With the exception of phenylethylamine, qualitatively similar effects were found with all other amines measured; their amounts were increased dose-dependently and the effects of deuterated phenelzine were greater than those of phenelzine. Rat cerebral MAO activity was inhibited dose-dependently by phenelzine and by deuterated phenelzine. Type A MAO was inhibited more than type B, and deuterated phenelzine inhibited both types more than did phenelzine. The present study shows that the efficacy of phenelzine was increased about 5-fold by deuteration, that deuterated phenelzine increased tryptamine, m-tyramine and p-tyramine levels much more than it did the other monoamines, that phenylethylamine levels were least affected by the drug treatments, and that deuterated phenelzine inhibited MAO more than did phenelzine.
Dyck
L E
LE
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Juorio
A V
AV
Durden
D A
DA
Boulton
A A
AA
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010624:Phenelzine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D001679:Biogenic Amines; D008996:Monoamine Oxidase Inhibitors; D014443:Tyrosine; D014364:Tryptophan; D008995:Monoamine Oxidase; D010624:Phenelzine