Effect of Chronic Deuterated and Non-deuterated Phenelzine on Rat Brain Monoamines and Monoamine Oxidase

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1988 Mar 1

PMID 3393230

Authors

L E Dyck

A V Juorio

D A Durden

A A Boulton

Affiliations

Soon will be listed here.

Abstract

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.

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