Ahlskog J E, Muenter M D, Bailey P A, Miller P M
Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905.
Clin Neuropharmacol. 1991 Jun;14(3):214-27. doi: 10.1097/00002826-199106000-00004.
The potent and selective dopamine D-2 agonist, MK-458 [PHNO; (+)-4-propyl-9-hydroxynaphthoxazine] was administered as monotherapy to nine patients with Parkinson's disease in a double-blind, placebo-controlled 12-week investigation; ten other patients were randomized to placebo. MK-458 was formulated as a controlled-release preparation, using a hydroxypropyl methylcellulose-lactase (HPMC) matrix. Patients receiving MK-458/HPMC improved on a variety of measures of parkinsonism, compared to their baseline scores; in contrast, only trivial improvement was seen within the placebo group. We subsequently compared the anti-Parkinson response to MK-458/HPMC with the response to chronic carbidopa/levodopa monotherapy in an open label trial. Carbidopa/levodopa improved parkinsonism to a significantly greater degree than MK-458/HPMC. Doses of MK-458 used in these studies (up to 60 mg per day) were substantially higher than those in previously reported preliminary studies of this medication. We conclude that monotherapy with MK-458/HPMC results in a significant anti-Parkinson effect; however, the response falls short of that seen with carbidopa/levodopa.
强效选择性多巴胺D-2激动剂MK-458[PHNO；(+)-4-丙基-9-羟基萘并恶嗪]在一项双盲、安慰剂对照的12周研究中作为单一疗法给予9例帕金森病患者；另外10例患者被随机分配至安慰剂组。MK-458被配制成控释制剂，使用羟丙基甲基纤维素-乳糖酶（HPMC）基质。与基线评分相比，接受MK-458/HPMC的患者在帕金森病的多种测量指标上有所改善；相比之下，安慰剂组仅出现轻微改善。随后，我们在一项开放标签试验中比较了MK-458/HPMC与慢性卡比多巴/左旋多巴单一疗法的抗帕金森反应。卡比多巴/左旋多巴改善帕金森病的程度明显大于MK-458/HPMC。这些研究中使用的MK-458剂量（每日高达60毫克）远高于此前该药物初步研究中的剂量。我们得出结论，MK-458/HPMC单一疗法可产生显著的抗帕金森效应；然而，其反应不如卡比多巴/左旋多巴。
