Oxidant-mediated electronic excitation of imipramine

Michael A. Trush, Mark J. Reasor, Mark E. Wilson, Knox VanDyke

Research output: Contribution to journalArticle

Abstract

The interaction of imipramine with both resting and zymosan-activated human polymorphonuclear leukocytes (PMNs) resulted in the generation of chemiluminescence (CL). This CL was not accompanied, however, by an enhanced release of Superoxide anion. CL was also observed following the interaction of imipramine with either a xanthine oxidase or a horseradish peroxidase catalyzed system. Collectively, these observations support the concept that the CL elicited from these interactions is reflective of the electronic excitation of the imipramine molecule. In contrast to the response seen with PMNs, addition of imipramine to resting alveolar macrophages (AMs) failed to yield CL. However, CL from imipramine was observed with resting AMs upon supplementation with exogenous horseradish peroxidase. The lack of response with control AMs and the significant inhibition of the imipramine-PMN CL by the myeloperoxidase inhibitor azide suggests that a peroxidase-derived oxidant facilitated the oxidation of imipramine, yielding a product in an electronically excited state. In addition to PMNs, CL was elicited from imipramine by rat or rabbit liver microsomes, suggesting that PMNs may be a useful model system to predict a xenobiotic effect on the CL response elicited by other cellular oxidantgenerating systems. Moreover, these observations underscore the possibility that the metabolic activation of drugs by PMNs may be of pharmacologic-and toxicologic importance.

Original languageEnglish (US)
Pages (from-to)1401-1410
Number of pages10
JournalBiochemical Pharmacology
Volume33
Issue number9
DOIs
StatePublished - May 1 1984

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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    Trush, M. A., Reasor, M. J., Wilson, M. E., & VanDyke, K. (1984). Oxidant-mediated electronic excitation of imipramine. Biochemical Pharmacology, 33(9), 1401-1410. https://doi.org/10.1016/0006-2952(84)90405-2