ON ABSORPTION AND METABOLISM OF IMIPRAMINE BY RAT BRAIN AFTER SINGLE AND REPEATED DOSES

A method is given for extraction and quantitative determination of imipramine (Tofranil®) and some of its metabolites in the brain tissue. The recovery of imipramine added to brain tissue/amount extracted from the brain was determined for imipramine, desmethylimipramine, didesmethylimipramine and iminodibenzyl. The uptake and metabolism of imipramine in the rat brain were determined after administration of a single dose. The imipramine level in the brain reached a maximum one hour after i.p. administration, whereas after subcutaneous injection the maximum is only reached after 2 hours. In either case only 0.2% of the imipramine given is absorbed by the brain. In none of the cases were metabolites of imipramine found after the short time tests. In contrast to imipramine, desmethylimipramine (Pertofran®) is found in the rat brain only after a long period (4 hours). No accumulation of the drug in the brain was observed after daily administration of imipramine for 10 days and under the test conditions mentioned. A level, amounting to 2 μg imipramine/brain, is reached as early as the first day of administration. Desmethylimipramine appeared for the first time on the third test day, and its level remained practically unchanged from the third to the tenth day at 1 μg/brain. © 1969 Springer-Verlag.