Adachi Kouichi, Miwa Hideto, Kusumoto Haruko, Shimazu Seiichiro, Kondo Tomoyoshi
Department of Neurology, Wakayama Medical University, Wakayama, Japan.
J Pharmacol Sci. 2006 Aug;101(4):286-92. doi: 10.1254/jphs.fp0051085. Epub 2006 Aug 5.
Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular striatal dopamine (DA) level in awake rats treated with L-DOPA and/or selegiline using a microdialysis method. Rats given 10 mg/kg, i.p. per day selegiline for 7 days were administered with a single dose of 100 mg/kg, i.p. L-DOPA 0 (3 h), 1, 3, 7, 14, 21, or 28 days after the last selegiline treatment. Carbidopa was administered 0.5 h before L-DOPA administration. The significant increase in basal DA level before L-DOPA treatment persisted until 1 day after the last selegiline treatment, and the significant decrease in basal DOPAC level persisted for more than 28 days. Thus, selegiline affected DA catabolism for more than 28 days. Total monoamine oxidase (MAO) and MAO-B activities at day 0 decreased by 22% and 5.7%, respectively. The significant enhancement of L-DOPA-induced increase in DA level was observed until 3 days after the last selegiline treatment. Next, the effects of reducing L-DOPA dose by 25% were examined 3 h after the last selegiline treatment. A dose-dependent decrease in DA level was observed, indicating that DA level in selegiline-treated rats can be controlled by L-DOPA dose.
司来吉兰用作左旋多巴治疗的辅助药物。我们使用微透析方法研究了用左旋多巴和/或司来吉兰治疗的清醒大鼠纹状体细胞外多巴胺（DA）水平。每天腹腔注射10mg/kg司来吉兰，连续7天的大鼠，在最后一次司来吉兰治疗后0（3小时）、1、3、7、14、21或28天腹腔注射单剂量100mg/kg左旋多巴。在左旋多巴给药前0.5小时给予卡比多巴。左旋多巴治疗前基础DA水平的显著升高持续到最后一次司来吉兰治疗后1天，基础3,4-二羟基苯乙酸（DOPAC）水平的显著降低持续超过28天。因此，司来吉兰对DA分解代谢的影响超过28天。第0天总单胺氧化酶（MAO）和MAO-B活性分别降低了22%和5.7%。直到最后一次司来吉兰治疗后3天，仍观察到左旋多巴诱导的DA水平升高显著增强。接下来，在最后一次司来吉兰治疗后3小时检查将左旋多巴剂量降低25%的效果。观察到DA水平呈剂量依赖性下降，表明司来吉兰治疗的大鼠中的DA水平可通过左旋多巴剂量来控制。
