Fuxe K, Agnati L, Mascagni F, Kuga S, Helmer-Matyjek E, Goldstein M
Brain Res. 1985 Mar 4;328(2):325-32. doi: 10.1016/0006-8993(85)91044-3.
The effects of the 8-alpha-amino-ergoline CU 32-085 on central dopamine neuronal systems was investigated. Two h after administration of CU 32-085 a slight increase of dopamine levels was observed in the nucleus caudatus-putamen. Radioligand binding studies in vitro have shown that CU 32-085 has a low affinity for striatal dopamine receptors labeled by [3H]n-propylapomorphine or [3H]spiroperidol. However, CU 32-085 effectively displaces in vivo [3H]n-propylapomorphine and [3H]spiroperidol from their respective binding sites in the mouse striatum. Functional studies have shown that CU 32-085 elicits contralateral rotation in rats with unilateral 6-OH-dopamine induced lesions of the meso-striatal dopamine neurons, and ipsilateral rotation in rats with unilateral intrastriatal ibotenic acid lesions. CU 32-085 relieves tremor in monkeys with ventromedial tegmental lesions and produces only slight abnormal involuntary movements. The biochemical and functional studies suggest that CU 32-085 and/or its metabolite exerts central dopamine agonist activity in vivo. Studies in monkeys with ventromedial tegmental lesions suggest that CU 32-085 might be an effective antiparkinsonian agent which produces less dyskinesias than the other tested dopamine agonists.
研究了8-α-氨基麦角灵CU 32-085对中枢多巴胺神经元系统的作用。给予CU 32-085两小时后，尾状核-壳核中的多巴胺水平略有升高。体外放射性配体结合研究表明，CU 32-085对由[3H]正丙基阿扑吗啡或[3H]螺哌啶醇标记的纹状体多巴胺受体具有低亲和力。然而，CU 32-085能有效地在体内从小鼠纹状体中各自的结合位点取代[3H]正丙基阿扑吗啡和[3H]螺哌啶醇。功能研究表明，CU 32-085在单侧6-羟基多巴胺诱导中脑-纹状体多巴胺神经元损伤的大鼠中引发对侧旋转，在单侧纹状体内注射鹅膏蕈氨酸损伤的大鼠中引发同侧旋转。CU 32-085可缓解腹内侧被盖区损伤的猴子的震颤，且仅产生轻微的异常不自主运动。生化和功能研究表明，CU 32-085和/或其代谢产物在体内发挥中枢多巴胺激动剂活性。对腹内侧被盖区损伤的猴子的研究表明，CU 32-085可能是一种有效的抗帕金森病药物，与其他测试的多巴胺激动剂相比，其产生的运动障碍较少。
