Drug-specificity in the perturbation of pulmonary disposition of serotonin in rabbit in vivo

Pharmacology. 1983;27(5):289-97. doi: 10.1159/000137882.

Abstract

Previous work indicates that one consequence of the accumulation of several xenobiotics in the lung is compromised pulmonary disposition of 5-hydroxytryptamine (5-HT). In the present studies, we examined whether pulmonary accumulation of chlorpromazine (CPZ), propranolol (P), imipramine (IMP), and clomipramine (Cl-IMP) affected 5-HT disposition in rabbit lungs. Pulmonary extraction and metabolism of [14C]-5-HT during single pulmonary passage were examined using the reference indicator radioisotope dilution technique in male New Zealand albino rabbits. After control experiment, animals received CPZ or P (2.5, 5, or 10 mg/kg), IMP or Cl-IMP (0.25, 0.5 or 1.0 mg/kg) via the jugular vein. Pulmonary clearance was 83% of administered 5-HT. A significant proportion (28%) of total radioactivity in the bloodstream after single passage was recovered as 5-HIAA in control experiments. These values were reduced significantly to 70 and 20%, respectively upon prior administration of IMP (0.25 mg/kg). Cl-IMP was more effective in reducing these values further. CPZ and P were marginally effective at the highest dose. While prior administration of IMP and Cl-IMP resulted in pulmonary accumulation of both drugs, the latter accumulated to a significantly greater extent. These results suggest that Cl-IMP has higher affinity to the rabbit lung than IMP and may inhibit pulmonary uptake of 5-HT by competition for uptake and binding sites more than IMP.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chlorpromazine / pharmacology*
  • Clomipramine / pharmacology*
  • Imipramine / pharmacology*
  • Lung / drug effects
  • Lung / metabolism*
  • Male
  • Propranolol / pharmacology*
  • Rabbits
  • Radioisotope Dilution Technique
  • Serotonin / metabolism*

Substances

  • Serotonin
  • Propranolol
  • Clomipramine
  • Imipramine
  • Chlorpromazine