Abstract
Marked, dose-dependent elevation 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 60mg/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 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-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 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 MAO-A and MAO- B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 39-48 |
| Number of pages | 10 |
| Journal | Journal of Neural Transmission, Supplement |
| Issue number | 52 |
| State | Published - 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline). / Murphy, D. L.; Karoum, F.; Pickar, D.; Cohen, R. M.; Lipper, S.; Mellow, A. M.; Tariot, P. N.; Sunderland, T.
In: Journal of Neural Transmission, Supplement, No. 52, 1998, p. 39-48.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline)
AU - Murphy, D. L.
AU - Karoum, F.
AU - Pickar, D.
AU - Cohen, R. M.
AU - Lipper, S.
AU - Mellow, A. M.
AU - Tariot, P. N.
AU - Sunderland, T.
PY - 1998
Y1 - 1998
N2 - Marked, dose-dependent elevation 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 60mg/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 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-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 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 MAO-A and MAO- B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.
AB - Marked, dose-dependent elevation 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 60mg/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 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-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 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 MAO-A and MAO- B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.
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M3 - Article
SP - 39
EP - 48
JO - Journal of Neural Transmission, Supplement
JF - Journal of Neural Transmission, Supplement
SN - 0303-6995
IS - 52
ER -