Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline).
Marked, dose-dependent elevations in the urinary excretion of phenylethylamine, para-tyramine, and meta-tyramine were observed in depressed patients treated for three or more weeks with 10, 30, or 60 mg/day of the partially-selective inhibitor of MAO-B, selegiline (l-deprenyl). In comparative studies with other, structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A inhibitor used in doses of 90 mg/day for three or more weeks, produced elevations in these trace amines which were similar to those found with the highest dose of selegiline studied. Clorgyline, a selective inhibitor of MAO-A used in doses of 30 mg/day for three or more weeks (a dose/time regimen previously reported to reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) > 80%, indicating a marked inhibitory effect on MAO-A in humans in vivo) produced negligible changes in trace amine excretion. In comparison to recent studies of individuals lacking the genes for MAO-A, MAO-B, or both MAO-A and MAO-B, the lack of change in trace amine excretion in individuals with a mutation affecting only MAO-A is in agreement with the observed lack of effect of clorgyline in the present study. Selegiline produced larger changes in trace amines--at least at the higher doses studied--than found in individuals lacking the gene for MAO-B, in agreement with other data suggesting a lesser selectivity for MAO-B inhibition when selegiline was given in doses higher than 10 mg/day. Overall, trace amine elevations in individuals receiving the highest dose of deprenyl or receiving pargyline were approximately three to five-fold lower than the elevations observed in individuals lacking the genes for both MAO-A and MAO-B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.
Murphy
D L
DL
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA.
Karoum
F
F
Pickar
D
D
Cohen
R M
RM
Lipper
S
S
Mellow
A M
AM
Tariot
P N
PN
Sunderland
T
T
D001679:Biogenic Amines / Q000652:urine*; D002872:Chromosome Deletion; D003010:Clorgyline / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000652:urine*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D008297:Male; D008995:Monoamine Oxidase / Q000172:deficiency / Q000235:genetics; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D010293:Pargyline / Q000627:therapeutic use*; D010627:Phenethylamines / Q000652:urine; D012016:Reference Values; D012189:Retrospective Studies; D012642:Selegiline / Q000627:therapeutic use*; D014439:Tyramine / Q000652:urine; D014960:X Chromosome
D001679:Biogenic Amines; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012642:Selegiline; D010293:Pargyline; D008995:Monoamine Oxidase; C028169:3-tyramine; D003010:Clorgyline; D014439:Tyramine