Wyska Elzbieta, Szymura-Oleksiak Joanna, Opoka Włodzimierz, Baś Bogusław, Niewiara Ewa, Pomierny Lucyna, Dybała Małgorzata, Nowak Gabriel
Department of Pharmacokinetics, Collegium Medicum, Jagiellonian University, Medyczna 9, PL 30-688 Kraków, Poland.
Pol J Pharmacol. 2004 Jul-Aug;56(4):479-84.
Recent preclinical and clinical data indicate beneficial role of zinc in the antidepressant treatment. To evaluate the mechanism of interaction between zinc and antidepressants, in the present study we examined the brain zinc, imipramine and desipramine concentrations in mice treated with combinations of zinc and imipramine and subjected to the forced swim test. We have chosen doses of zinc (10 mg/kg) and imipramine (15 mg/kg) which we have previously found to be ineffective in the forced swim test when given alone. However, when administered jointly, a significant reduction in the immobility time in this test was demonstrated. In the present study, we demonstrated a significant ca. 60% reduction in the brain desipramine and non-significant reduction (ca. 40%) in brain imipramine concentrations in the group of animals treated with zinc plus imipramine compared with animals treated with imipramine alone. The brain zinc concentration in the zinc plus imipramine group was reduced when compared with the group treated with zinc or imipramine alone. Since there was no increase in brain imipramine/desipramine or zinc brain concentration after combined zinc and imipramine treatment, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between zinc and imipramine is responsible for behavioral effect in the forced swim test.
近期的临床前和临床数据表明锌在抗抑郁治疗中具有有益作用。为了评估锌与抗抑郁药之间的相互作用机制，在本研究中，我们检测了联合使用锌和丙咪嗪并接受强迫游泳试验的小鼠脑内锌、丙咪嗪和地昔帕明的浓度。我们选择了锌（10 mg/kg）和丙咪嗪（15 mg/kg）的剂量，此前我们发现单独给予这些剂量时在强迫游泳试验中无效。然而，联合给药时，该试验中的不动时间显著缩短。在本研究中，我们发现与单独给予丙咪嗪的动物相比，联合给予锌和丙咪嗪的动物组脑内地昔帕明浓度显著降低约60%，脑内丙咪嗪浓度降低不显著（约40%）。与单独给予锌或丙咪嗪的组相比，联合给予锌和丙咪嗪组的脑锌浓度降低。由于联合给予锌和丙咪嗪后，脑内丙咪嗪/地昔帕明或锌的脑浓度没有增加，数据表明锌和丙咪嗪之间的药效学而非药代动力学相互作用是强迫游泳试验中行为效应的原因。
