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Research Article| Volume 20, ISSUE 8, P858-865, August 1985

Opposite effects of chronic imipramine treatment on brain and urine MHPG levels in the rat

  • M.L. Sedlock
    Correspondence
    Address reprint requests to Dr. M. L. Sedlock, University of Pittsburgh, School of Pharmacy, Department of Pharmacology and Toxicology, 1100 Salk Hall, Pittsburgh, PA 15261.
    Footnotes
    Affiliations
    School of Pharmacy, Department of Pharmacology and Toxicology, Pittsburgh, PA, USA
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  • David J. Edwards
    Footnotes
    Affiliations
    University of Pittsburgh, School of Dental Medicine, Department of Pharmacology-Physiology, USA
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  • Author Footnotes
    1 We thank CIBA-Geigy for providing imipramine hydrochloride and Steven Knopf for performing the HPLC analysis.
DOI:https://doi.org/10.1016/0006-3223(85)90211-2
Opposite effects of chronic imipramine treatment on brain and urine MHPG levels in the rat
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      Abstract

      Acute imipramine (IMI; 20 mg/kg, ip) in rats decreased the brain concentration of 3-methoxy-4-hydroxyphenethylene glycol (MHPG), a metabolite of norepinephrine (NE), to 85% of control 24 hr after injection. In contrast, chronic IMI (20 mg/kg, ip, daily for 14 days) significantly raised brain MHPG levels to 123% of control, while reducing brain NE levels. Urinary MHPG levels were reduced by both acute and chronic IMI treatments, to 52% and 51%, respectively. These data suggest that the brain turnover of NE is reduced after acute IMI, but is elevated after chronic treatment. Although urinary levels of MHPG changed in parallel with brain levels following an acute administration of IMI, such was not the case after chronic administration. We conclude that caution must be used in extrapolating drug-induced changes in urinary metabolite levels to brain amine function.
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      Article info

      Publication history

      Received in revised form: February 20, 1985
      Received: December 10, 1984

      Footnotes

      ☆Supported in part by NIMH Grant MH-28340 (D.J.E.) and by an Eli Lilly-AFPE Fellowship (M.L.S.).

      Identification

      DOI: https://doi.org/10.1016/0006-3223(85)90211-2

      Copyright

      © 1985 Published by Elsevier Inc.

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