Potter Pamela E
Department of Pharmacology, Midwestern University/Arizona College of Osteopathic Medicine, Glendale, Arizona 85308-6813, USA.
J Am Osteopath Assoc. 2010 Sep;110(9 Suppl 8):S27-36.
Development of effective treatments for patients with Alzheimer disease has been challenging. Currently approved treatments include acetylcholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine hydrochloride. To investigate treatments in development for patients with Alzheimer disease, the author conducted a review of the literature. New approaches for treatment or prevention focus on several general areas, including cholinergic receptor agonists, drugs to decrease β-amyloid and tau levels, antiinflammatory agents, drugs to increase nitric oxide and cyclic guanosine monophosphate levels, and substances to reduce cell death or promote cellular regeneration. The author focuses on medications currently in clinical trials. Cholinergic agents include orthostatic and allosteric muscarinic M1 agonists and nicotinic receptor agonists. Investigational agents that target β-amyloid include vaccines, antibodies, and inhibitors of β-amyloid production. Anti-inflammatory agents, including nonsteroidal anti-inflammatory drugs, the natural product curcumin, and the tumor necrosis factor α inhibitor etanercept, have also been studied. Some drugs currently approved for other uses may also show promise for treatment of patients with Alzheimer disease. Results of clinical trials with many of these investigational drugs have been disappointing, perhaps because of their use with patients in advanced stages of Alzheimer disease. Effective treatment may need to begin earlier-before neurodegeneration becomes severe enough for symptoms to appear.
为阿尔茨海默病患者开发有效的治疗方法一直具有挑战性。目前已获批的治疗方法包括乙酰胆碱酯酶抑制剂和N-甲基-D-天冬氨酸受体拮抗剂盐酸美金刚。为了研究针对阿尔茨海默病患者正在研发的治疗方法，作者对相关文献进行了综述。治疗或预防的新方法集中在几个一般领域，包括胆碱能受体激动剂、降低β-淀粉样蛋白和tau蛋白水平的药物、抗炎药、增加一氧化氮和环磷酸鸟苷水平的药物，以及减少细胞死亡或促进细胞再生的物质。作者重点关注目前正在进行临床试验的药物。胆碱能药物包括体位性和变构性毒蕈碱M1激动剂以及烟碱受体激动剂。针对β-淀粉样蛋白的研究药物包括疫苗、抗体和β-淀粉样蛋白生成抑制剂。抗炎药，包括非甾体抗炎药、天然产物姜黄素和肿瘤坏死因子α抑制剂依那西普，也已得到研究。一些目前已获批用于其他用途的药物可能对治疗阿尔茨海默病患者也有前景。许多这类研究药物的临床试验结果令人失望，可能是因为它们用于阿尔茨海默病晚期患者。有效的治疗可能需要更早开始——在神经退行性变变得严重到足以出现症状之前。
