Effects of recombinant drug-specific single chain antibody Fv fragment on [3H]-desipramine distribution in rats

Weilin L. Shelver, Daniel E. Keyler, Gaofeng Lin, Michael P. Murtaugh, Michael C. Flickinger, Catherine A. Ross, Paul R. Pentel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Tricyclic antidepressant overdose can be reversed in rats by drug-specific antibody Fab fragments, but the required Fab dose may itself be toxic. We studied the potential use of a smaller, recombinant desipramine (DMI)-specific single chain Fv fragment (B9-sFv) for this purpose. Anesthetized rats received a tracer (subtoxic) dose of [3H]-DMI followed in 15 min by B9-IgG, B9-Fab, B9-sFv (0.1 μmol of binding sites), or BSA. Each of the active treatments produced a rapid and substantial increase in the serum radiolabel concentration, whereas BSA did not (P < 0.001). The increase in serum radiolabel concentration 1 min after treatment was 13.3-fold with B9-IgG, 10.0-fold with B9-Fab and 7.3-fold with B9-sFv. Serum antibody concentrations were also highest after B9-IgG and lower with B9-Fab or B9-sFv. The 24-hr urinary excretion of radiolabel did not differ among groups, but was extensive even in the BSA group and probably represented the excretion of DMI metabolites. B9-sFv concentrations in urine or buffer at 37° declined by >90% over 24 hr, but this fragment was much more stable in serum, retaining 70% of its activity after 96 hr. These data demonstrate that B9-sFv can alter markedly the distribution of [3H]-DMI in vivo. The rapidity of this effect, and its magnitude in comparison with Fab fragment or IgG, suggest that further study of B9-sFv as a treatment of DMI overdose is warranted.

Original languageEnglish (US)
Pages (from-to)531-537
Number of pages7
JournalBiochemical Pharmacology
Volume51
Issue number4
DOIs
StatePublished - Feb 23 1996

Bibliographical note

Funding Information:
We are grateful to Dr. Susan Pond for supplying the B9 hybridoma clone. This work was supported by PHS Grants MH42799 and 5T32DA07097, and a grant from Hennepin Faculty Associates.

Keywords

  • Antibody
  • Immunotherapy
  • Immunotoxicology
  • Overdose
  • SFv fragment
  • Tricyclic antidepressant

Fingerprint

Dive into the research topics of 'Effects of recombinant drug-specific single chain antibody Fv fragment on [<sup>3</sup>H]-desipramine distribution in rats'. Together they form a unique fingerprint.

Cite this