Influences of Various Emotional Situations on Pharmaokinetics and Pharmacodynamics

一些用于临床治疗的药物的药动学可能受到各种情绪状况的影响。在以往的研究中，我们研究了血管扩张剂、抗癫痫药等药物在药物吸收过程中受到各种情绪应激的药代动力学影响。本研究研究了不同情绪情境对血管扩张剂尼可地尔和抗癫痫药物唑尼沙胺在大鼠和小鼠体内的药代动力学和药效学的影响。1)研究了暴露于新环境引起的轻中度情绪变化对大鼠血浆药物浓度药代动力学的影响。转入新家笼组口服尼可地尔10 mg/kg后测定的血浆尼可地尔浓度与对照组相比显著降低。但唑尼沙胺浓度没有变化。2)大鼠下丘脑外侧刺激诱导的自我刺激奖励轻微抑制口服尼可地尔的吸收，促进其排泄。另一方面，固定应力不仅抑制了药物的吸收过程，而且抑制了药物的排泄过程。固定化应激使小肠推进活性降低。3)同时研究了唑尼沙胺在情绪应激小鼠体内的药动学和药效学。在给药小鼠中，固定应激可延长MES引起的强直伸展（TE）持续时间。在唑胺（20或50 mg/kg， p.o.）给药组中，固定应激降低了TE的发生率，但与非应激组相比，药物血浆浓度没有变化。这表明不同的情绪状况可能会影响临床治疗中某些药物的药代动力学和药效学。

The pharmakoninetics of some drugs used in clinical therapy may be influenced by various emotional situations. In the previous studies, we have investigated the pharmacokinetics of drugs like vasodilators, and antiepileptics, were influenced by various kinds of emotional stress in the drug absorption process. In the present study, the influences of various kinds of emotional situations on pharmacokinetics and pharmacodynamics of nicorandil, a vasodilator, and zonisamide, an antiepileptic drug, were investigated in rats and mice. 1) Influences of mild and moderate emotional changes induced by exposure to a new environment on the pharmacokinetics of plasma drug concentration were studied in rats. The plasma nicorandil concentration determined after oral administration of nicorandil at a close of 10 mg/kg in the group transferred to the new home cage decreased significantly in comparison to the control group. However, zonisamide concentration did not change. 2) The self-stimulation reward induced by lateral hypothalamic stimulation in rats slightly inhibited the absorption of oral nicorandil and facilitated the excretion. On the other band, the immobilization stress inhibited not only the drug absorption process but also the excretion process. The propulsive activity of in small intestinal intestine was depressed by immobilization stress. 3) Pharmacokinetics and pharmacodynamics of zonisamide were at the same time investigated in mice which were loaded emotional stress. In the vehicle administered mice, the duration of tonic extension (TE) induced by MES was prolonged by immobilization stress. In the zonlsamide (20 or 50 mg/kg, p.o.) administered group, the incidence of TE was depressed by immobilization stress although the drug plasma concentrations was not changed in comparison to non-stressed group. These indicate that various emotional situations may influence the pharmacokinetics and pharmacodynamics of some drugs used in clinical therapy.