THYROID ACCUMULATION AND ADVERSE-EFFECTS OF IMIPRAMINE AND DESIPRAMINE IN RATS AFTER LONG-TERM ADMINISTRATION

The respective adverse effects of imipramine and desipramine on serum thyroid hormone levels and their accumulation in thyroid were investig ated in male Wistar rats. Two groups of 30 rats were gavaged for 4 wee ks with 30 mg/kg/day imipramine hydrochloride (IMI) or desipramine hyd rochloride (DESI), while the control group (12 rats) received the arab ic gum vehicle only. In the IMI-treated group, the serum thyroxine (T- 4) level significantly decreased (by 13%) and IMI and its metabolite D ESI were accumulated in the thyroid, as pointed out by mean thyroid-to -serum concentration ratios close to 12 and 8, respectively. In the DE SI-treated group, the mean thyroid-to-serum concentration ratio of the drug was close to 14, and significant decreases in both serum T-4 (-2 0%) and triiodothyronine serum levels (-14%) were found. The accumulat ion of antidepressant drugs in the thyroid was more pronounced and the thyroid serum levels were even lower after DESI administration than a fter IMI administration. These results are in favour of an antithyroid action of IMI and DESI due to the formation of a complex in the thyro id between molecular iodine and the drugs or metabolites.