Imipramine-caused interference with levodopa absorption from the gastrointestinal tract in rats

Rats treated for 3 or 30 days with imipramine (30 mg/kg) have impaired absorption of a single dose of 14C-levodopa. Treated animals retain larger amounts of radioactivity in their gastric lumen and this interfers with delivery of levodopa to intestinal absorptive sites. Tissues of treated animals have lower levels of radioactivity than controls and urinary excretion of radioactivity is also lessened. Imipramine does not interfere with uptake of levodopa by everted sacs of rat jejunum. Imipramine does, however, interfere with the transit of radioactivity through the gastrointestinal tract of rats, since treated animals have lower ileal radioactivity than controls. Lower relative concentration of levodopa metabolites in gastric fluid and tissue may reflect an interference of uptake of levodopa by gastric enterochromaffin-like cells.