Pharmacological and Pharmacokinetic Studies on Anti-spastic Drugs

抗痉挛药物的药理及药代动力学研究

• 批准号: 62480420
• 负责人: FUKUDA Hideomi
• 金额: $ 3.39万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480420/
• 关键词: antispastic drugs; muscle relaxants; noradrenaline; spinal cord; 2ーデオキシグルコース法; バクロフェン; スリクロン; αアゴニスト; αアンタゴニスト

Antispastic drugs have been used for the relief of elevated muscle tone in spastic paralysis and spinal cord injury. In the present research, the precise mechanisms of action of antispastic drugs have been studied.1. Using spinal cord slices isolated from adult rats,alpha_1-agonistic action has been shown to enhance the spinal motorneuron activity.2.alpha_2-Agonists reduced noradrenaline release from descending noradrenergic terminals in the spinal cord. These results suggest that alpha_1-agonistic action elevates muscle tone and that muscle relaxation caused by alpha_2-agonists is due to the decrease in noradrenaline release in the spinal cord.3. The method which can be used for evaluation of the site of action (spinal or supraspinal level) of antispastic drugs was developed.4. The mechanism of antispastic drugs was studied using nystagmus in rabbits.5. 2-Deoxyglucose method was improved using [^3H]-3-O-methylglucose and [^<14>C]-2-deoxyglucose. The time required for measurement of glucose utilization was shortened to 5-10 min from 45 min. This method can be used for study of site of action of antispastic drugs.

解痉药已被用于缓解痉挛性瘫痪和脊髓损伤中肌张力升高。在本研究中，解痉药的确切作用机制已被研究。用成年大鼠的脊髓切片，α_1激动剂能增强脊髓运动神经元的活性。2. α_2激动剂能减少脊髓中降去甲肾上腺素能末梢释放去甲肾上腺素。这些结果表明，α_1-激动剂的作用，提高肌肉张力和α_2-激动剂引起的肌肉松弛是由于减少去甲肾上腺素释放的脊髓。建立了一种可用于评价解痉药作用部位（脊髓或棘上水平）的方法.采用家兔眼震实验研究解痉药物的作用机制. 2-用[^3H]-3-O-甲基葡萄糖和[<14>^3C]-2-脱氧葡萄糖改进了脱氧葡萄糖法。测定葡萄糖利用率所需时间由45 min缩短为5-10 min，可用于解痉药作用部位的研究。

项目成果

H.Ono: Biomedical Res.9. 169-176 (1988)

H.Ono：生物医学研究9。

Ono, H.: "alpha_2-Agonists-induced reduction of noradrenaline release from descending noradrenergic terminals in rat spinal cord: Functional relation to spinal motor system." Biomedical Res.9. 169-176 (1988)

Ono, H.：“α_2 激动剂诱导大鼠脊髓中去甲肾上腺素能末梢下降的去甲肾上腺素释放减少：与脊髓运动系统的功能关系。”

H.Ono: Arzneim-Forschung. 37. 384-388 (1987)

H.Ono：Arzneim-Forschung。

T.Kaneko: Arch.int.Pharmacodyn.287. 203-210 (1987)

T.Kaneko：Arch.int.Pharmacodyn.287。

M.Ishikawa: General Pharmacol. 20. 47-51 (1989)

M.Ishikawa：通用药理学。