Cotzias G C, Papavasiliou P S, Tolosa E S, Mendez J S, Bell-Midura M
N Engl J Med. 1976 Mar 11;294(11):567-72. doi: 10.1056/NEJM197603112941101.
To avoid the main drawbacks of prolonged treatment with levodopa (involuntary movements and the "on-off" phenomenon), we administered apomorphine by mouth to 14 patients with Parkinson's disease. This treatment caused azotemia, which we circumvented by switching to N-propylnoraporpine, whose nephrotoxic dose (80 mg six times per day) was larger than its therapeutic dose (10 to 15 mg six times per day). Slowly increasing doses induced significant improvement (P less than 0.005) in all 24 patients studied, transitory mental aberrations in seven, and release of growth hormone in three patients tested. In patients previously on prolonged levodopa administration, the dyskinesia and "on-off" phenomenon were almost identical with N-propylnoraporphine, but both drawbacks were reduced or abolished in six patients by coadministration of alpha-methyldopa hydrazine plus levodopa. This coadministration seemed to abolish tachyphylaxis. We conclude that N-propylnoraporphine is very useful in the treatment of Parkinson's disease.
为避免左旋多巴长期治疗的主要弊端（不自主运动和“开-关”现象），我们对14例帕金森病患者口服阿扑吗啡进行治疗。这种治疗导致氮质血症，我们通过改用N-丙基去甲阿朴吗啡来解决这一问题，其肾毒性剂量（每日6次，每次80毫克）大于治疗剂量（每日6次，每次10至15毫克）。缓慢增加剂量使所有24例研究患者均有显著改善（P<0.005），7例出现短暂精神错乱，3例接受测试的患者生长激素释放。在先前长期服用左旋多巴的患者中，使用N-丙基去甲阿朴吗啡时的运动障碍和“开-关”现象与左旋多巴几乎相同，但在6例患者中，联合使用α-甲基多巴肼加左旋多巴可减轻或消除这两个弊端。这种联合用药似乎消除了快速耐受性。我们得出结论，N-丙基去甲阿朴吗啡在帕金森病治疗中非常有用。
