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 (1-deprenyl). In comparative studies with other, structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A inhibitor used in doses of 90mg/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 30mg/ day for three or more weeks (a dose/time regimen previously reported to reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4hydroxyphenylethyleneglycol (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 10mg/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 MAOA and MAO-B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.
KeywordsMonoamine Oxidase Trace Amine Deficient Subject Norrie Disease Inhibitor Clorgyline
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