Influences of Various Emotional Situations on Pharmaokinetics and Pharmacodynamics

各种情绪状况对药代动力学和药效学的影响

• 批准号: 09672325
• 负责人: GOMITA Yutaka
• 金额: $ 1.92万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672325/
• 关键词: Clinical used drugs; Phaumacokinetics; Pharmacodynamics; Cigarette-smoke; Nicotine; Animals; Plasma concentration; Emotional stress; 医薬品; 体内動態; ニコランジル; ゾニサミド; 情動ストレス; 快・不快

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.

临床治疗中使用的一些药物的药代动力学可能会受到各种情绪情况的影响。在前期的研究中，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影响的药代动力学。本研究在大鼠和小鼠中研究了各种情绪状况对血管扩张剂尼可地尔和抗癫痫药唑尼沙胺的药代动力学和药效学的影响。 1)在大鼠中研究了暴露于新环境引起的轻度和中度情绪变化对血药浓度药代动力学的影响。转入新笼的组以10mg/kg结束口服尼可地尔后测定的血浆尼可地尔浓度与对照组相比显着降低。然而，唑尼沙胺浓度没有变化。 2)大鼠下丘脑外侧刺激引起的自我刺激奖赏轻微抑制口服尼可地尔的吸收并促进排泄。另一方面，固定应力不仅抑制药物吸收过程，而且抑制排泄过程。小肠的推进活性因固定应激而受到抑制。 3)在承受情绪应激的小鼠中同时研究了唑尼沙胺的药代动力学和药效学。在给予媒介物的小鼠中，MES诱导的强直延伸（TE）的持续时间因固定应激而延长。在唑胺（20 或 50 mg/kg，口服）给药组中，尽管与非应激组相比，药物血浆浓度没有变化，但固定应激降低了 TE 的发生率。这些表明各种情绪状况可能会影响临床治疗中使用的一些药物的药代动力学和药效学。

项目成果

Y.Hashimoto H.Kawasaki Y.Gomita: "Influences of emotional changes induced by exposure to new circurnsfances on pharmacokinetics of plasma durg concentration in rats"ACTA Medica Okayama. (submitted).

Y.Hashimoto H.Kawasaki Y.Gomita：“暴露于新环境引起的情绪变化对大鼠血浆药物浓度药代动力学的影响”冈山医学报。

Yasuhiko Hashimoto, et al.: "Influences of emotional changes induced by exposure to new circumstances on pharmacokinetics of plasma drug concentration in rats"Acta Medica Okayama. (Submitted).

Yasuhiko Hashimoto 等人：“暴露于新环境引起的情绪变化对大鼠血浆药物浓度药代动力学的影响”冈山医学报。