title: Drug-specificity in the perturbation of pulmonary disposition of serotonin in rabbit in vivo.
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.
mesh_terms: D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits; D011865:Radioisotope Dilution Technique; D012701:Serotonin / Q000378:metabolism*
chemical_list: D012701:Serotonin; D011433:Propranolol; D002997:Clomipramine; D007099:Imipramine; D002746:Chlorpromazine