| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
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.
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