Pharmacological and Pharmacokinetic Studies on Anti-spastic Drugs

抗痉挛药物已被用于缓解痉挛瘫痪和脊髓损伤时肌肉张力的升高。在本研究中，我们对解痉剂的确切作用机制进行了研究。在分离的成年大鼠脊髓切片上，α_1激动剂可增强脊髓运动神经元的活性。2.α_2激动剂可减少去甲肾上腺素从脊髓去甲肾上腺素能神经末梢释放。这些结果提示，α_1激动剂的作用可提高肌肉张力，α_2激动剂引起的肌肉松弛是由于脊髓去甲肾上腺素释放减少所致。建立了可用于评价抗痉挛药物作用部位(脊髓或棘上水平)的方法。利用兔眼球震颤模型，研究解痉剂的作用机制。对2-脱氧葡萄糖法进行了改进，加入了[~3H]-3-O-甲基葡萄糖和[^&lt；14&gt；C]-2-脱氧葡萄糖。测量葡萄糖利用率所需的时间从45分钟缩短到5-10分钟。该方法可用于解痉剂作用部位的研究。

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.