Rousseau A, Marquet P, Lagorce J F, Sauvage M F, Buxeraud J, Lachâtre G, Raby C
Department of Biophysics, Faculty of Pharmacy, University Hospital, Limoges, France.
Pharmacology. 1998 Nov;57(5):242-8. doi: 10.1159/000028248.
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.
在雄性Wistar大鼠中研究了丙咪嗪和地昔帕明对血清甲状腺激素水平及其在甲状腺中蓄积的各自不良影响。两组各30只大鼠分别以30毫克/千克/天的盐酸丙咪嗪（IMI）或盐酸地昔帕明（DESI）灌胃4周，而对照组（12只大鼠）仅接受阿拉伯胶水溶液。在IMI治疗组中，血清甲状腺素（T4）水平显著降低（降低13%），并且IMI及其代谢产物DESI在甲状腺中蓄积，甲状腺与血清浓度比的平均值分别接近12和8即表明了这一点。在DESI治疗组中，药物的甲状腺与血清浓度比平均值接近14，并且发现血清T4（降低20%）和血清三碘甲状腺原氨酸水平（降低14%）均显著降低。DESI给药后抗抑郁药在甲状腺中的蓄积更为明显，且甲状腺血清水平比IMI给药后更低。这些结果支持IMI和DESI具有抗甲状腺作用，这是由于分子碘与药物或代谢产物在甲状腺中形成了复合物。
