Comparison of neurochemical effects of the monoamine oxidase inhibitors phenelzine, moclobemide and brofaromine in the rat after short- and long-term administration.
BACKGROUND
Chronic administration of several irreversible monoamine oxidase (MAO) inhibitors induces a down-regulation of tryptamine and 5-hydroxytryptamine(2) receptors in rat brain, but there is a paucity of information available on the effects of reversible MAO-A inhibitors on these receptors.


METHODS
Acute and chronic experiments were conducted in rats and the effects of the irreversible monoamine oxidase inhibitor, phenelzine and the reversible MAO type-A inhibitors, moclobemide and brofaromine, on tryptamine and 5-hydroxytryptamine(2) receptors were analysed using radioligand binding techniques. In addition, activities of MAO-A and -B were determined radiochemically and brain and/or urine levels of tryptamine, 5-hydroxytryptamine, 3-methoxy-4-hydroxyphenylglycol (MHPG), beta-phenylethylamine, brofaromine and moclobemide were determined by chromatographic procedures.


RESULTS
After 30 days of administration, moclobemide and brofaromine selectively inhibited brain MAO-A activity and phenelzine inhibited MAO-A and -B to equal extents. All three drugs caused a significant down-regulation of tryptamine receptors, whereas only phenelzine significantly down-regulated 5-hydroxytryptamine(2) receptors. In a comparison of phenelzine and brofaromine, both caused marked elevations of urinary tryptamine and decreases of urinary MHPG levels, while only phenelzine increased beta-phenylethylamine levels. After 14 days of administration, phenelzine, but not moclobemide or brofaromine, significantly increased levels of tryptamine in brain; all three drugs significantly increased 5-HT levels.


CONCLUSIONS
24-h urine samples were not collected for moclobemide-treated animals and brain levels of tryptamine were not measured after 30-day administration.


CONCLUSIONS
These studies revealed marked neurochemical differences among phenelzine, moclobemide and brofaromine which could contribute to their actions in the clinical setting.
Urichuk
L J
LJ
Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Canada.
Allison
K
K
Holt
A
A
Greenshaw
A J
AJ
Baker
G B
GB
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D015536:Down-Regulation / Q000187:drug effects; D008134:Long-Term Care; D008297:Male; D020912:Moclobemide / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010624:Phenelzine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects
D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D011985:Receptors, Serotonin; C038213:brofaromine; D008995:Monoamine Oxidase; D010624:Phenelzine; D020912:Moclobemide