Summary
The 2 major metabolites of norepinephrine (NE), 3,4-dihydroxyphenylglycol-sulphate (DOPEG-SO4) and free plus conjugated 3-methoxy-4-hydroxyphenylglycol (total-MOPEG), both their endogenous concentrations and their accumulation from the NE-precursors 3H-tyrosine or 3H-dopamine, were determined in the whole rat brain to assess the effect of chronic treatment with desipramine (DMI), imipramine and amitriptyline. DOPEG-SO4 was decreased 2 h and 24 h after the last administration of DMI (10 mg/kg twice daily for 4, 10 or 20 days) or imipramine (10 mg/kg twice daily for 10 days). When measured within 24 h after the last dose of DMI or imipramine, several schedules resulted in reduced accumulation of total-3H-MOPEG and 3H-NE, while 3H-NE and MOPEG were unchanged in the remaining schedules. These results indicate that DMI retains its ability to decrease NE-turnover over a period of 20 days of treatment. Forty-eight hours or 72 h after the last administration of desipramine and imipramine an “overshoot” was observed in NE-metabolism, consisting of increased levels of total-3H-MOPEG and endogenous total-MOPEG; DOPEG-SO4 was some-times concomitantly increased. The “overshoot” was more consistent after 20 or 10 days of treatment than after 4 days of treatment. This finding, together with a tendency to partial tolerance to the metabolite decreasing effects of DMI, indicate that adaptive changes occur in the NE system after treatment for 10–20 days with DMI or imipramine.
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Abbreviations
- NE:
-
norepinephrine
- DOPEG:
-
3,4-dihydroxyphenylglycol
- DOPEG-SO4 :
-
DOPEG sulphate ester
- MOPEG:
-
3-methoxy-4-hydroxyphenylglycol
- total-MOPEG:
-
free plus conjugated MOPEG
- DOPAC:
-
3,4-dihydroxyphenylacetic acid
- HVA:
-
homovanillic acid
- NM:
-
normetanephrine
- DA:
-
dopamine
- DMI:
-
desipramine
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Nielsen, M., Bræstrup, C. Chronic treatment with desipramine caused a sustained decrease of 3,4-dihydroxyphenylglycol-sulphate and total 3-methoxy-4-hydroxyphenylglycol in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 87–92 (1977). https://doi.org/10.1007/BF00505083
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DOI: https://doi.org/10.1007/BF00505083