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 investigated in male Wistar rats. Two groups of 30 rats were gavaged for 4 weeks with 30 mg/kg/day imipramine hydrochloride (IMI) or desipramine hydrochloride (DESI), while the control group (12 rats) received the arabic gum vehicle only. In the IMI-treated group, the serum thyroxine (T4) level significantly decreased (by 13%) and IMI and its metabolite DESI were accumulated in the thyroid, as pointed out by mean thyroid-to-serum concentration ratios close to 12 and 8, respectively. In the DESI-treated group, the mean thyroid-to-serum concentration ratio of the drug was close to 14, and significant decreases in both serum T4 (-20%) and triiodothyronine serum levels (-14%) were found. The accumulation of antidepressant drugs in the thyroid was more pronounced and the thyroid serum levels were even lower after DESI administration than after IMI administration. These results are in favour of an antithyroid action of IMI and DESI due to the formation of a complex in the thyroid between molecular iodine and the drugs or metabolites.
Rousseau
A
A
Department of Biophysics, Faculty of Pharmacy, University Hospital, Limoges, France.
Marquet
P
P
Lagorce
J F
JF
Sauvage
M F
MF
Buxeraud
J
J
Lachâtre
G
G
Raby
C
C
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D003891:Desipramine / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism; D007099:Imipramine / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013963:Thyroid Hormones / Q000097:blood*
D000929:Antidepressive Agents, Tricyclic; D013963:Thyroid Hormones; D007099:Imipramine; D003891:Desipramine