The development of chronic pain is thought to involve changes in the synaptic excitability of the NMDA receptor, that are partially mediated by excitatory amino acids such as glutamate.^74-77 Results from clinical studies of memantine in neuropathic pain are varying.^75-78

Investigations that used memantine at dosages up to 80 mg/day, con?rmed that no de?nitive conclusion can yet be made with regards to ef?cacy of memantine in control of neuropathic pain associated with diabetic neuropathy.⁷⁹ On the other hand, in post herpetic neuralgia, memantine-treated patients had signi?cantly lower pain (p=0.002) than placebo-treated patients, based on the primary ef?cacy parameter of change from baseline in the weekly mean of the daily average pain rating throughout the study (Study MD-20).⁷⁹

Memantine is thought to act as a neuroprotective agent in glaucoma by preventing the excessive glutamate NMDA receptor activation that may contribute to the damage of the retinal nerve cells.⁸⁰ Animal models have already revealed that memantine can protect against retinal cell loss.⁸¹

The results of Phase III trials did not support a consistent bene?cial effect of memantine on the progression of glaucoma, compared with placebo.⁸²

Glutamate neurotoxicity is regarded as a potential factor in the neurodegeneration found in Huntington’s disease.⁸³ In a 2-year, multicentre trial, the effectiveness of memantine (up to 30 mg/day) was investigated in 27 patients with Huntington’s disease.⁸³ The results of this preliminary investigation indicated that memantine may slow disease progression.⁸³

Preclinical studies have shown that glutamate excitation may play a part in neuronal cell death in Parkinson’s disease (PD).⁸⁴ In addition, animal models of PD have indicated that glutamate antagonists have anti-akinetic effects.⁸⁴ Therefore, glutamate antagonists such as memantine, have been cited as candidates for treating the symptoms of PD, as well as slowing disease progression,^84,85 and the NMDA-receptor antagonist amantadine is already used in PD.⁸⁶

In a clinical study of 12 patients with idiopathic PD, memantine improved PD symptoms – an effect that appears independent of current dopaminergic therapies.⁸⁷ There are con?icting reports of whether memantine is able to improve the drug-induced dyskinesias that are a characteristic feature of long-term dopaminergic treatment of PD.^86,87

There are some case reports that memantine may be effective also in dementia associated with Parkinson’s disease (PDD),^86,88 and a study has been initiated to evaluate the effects of memantine in PDD. There are also numerous case reports of the effect of memantine in patients with dementia with Lewy bodies (DLB), indicating that the symptomatic effect is variable.^89-91

Recent research suggests that there is increased phospholipid metabolism in the anterior cingulate area of people with schizophrenia.⁹² This may be supportive evidence for a neurodegenerative mechanism in schizophrenia.⁹²

There are a few case reports of the use of memantine in schizophrenia,^93,94 indicating some therapeutic bene?ts of memantine in patients with schizophrenia. However, a recent double-blind, placebo-controlled evaluation of the safety and ef?cacy of memantine as adjunctive treatment to atypical antipsychotic medications in schizophrenia showed no signi?cant difference between memantine- and placebo-treated patients for the primary ef?cacy parameter, PANSS total score (Study MD-29).⁷⁹

 

We translated the file about Parkinsonism from English into Chinese.

 

慢性疼痛的出现被认为与NMDA受体的突触兴奋性改变有关，这一个过程部分由兴奋性氨基酸例如谷氨酸盐介导。 ^74-77美金刚治疗神经性疼痛的临床研究结果差异较大。^75-78

剂量为80mg/天的美金刚研究证实：关于美金刚控制糖尿病神经性病变相关的神经性疼痛的治疗效果尚不能得出确切的结论⁷⁹。另一方面，对带状疱疹后遗神经痛，基于主要有效性参数整个研究期间每天疼痛程度的周均数自基线的改变，与安慰剂组相比，美金刚能显著减轻患者疼痛（p=0.002）（研究 MD-20）。⁷⁹

美金刚被认为在治疗青光眼的过程中具有神经保护作用，这通过阻止过度的谷氨酸NMDA受体激活而发挥作用，因为过度的谷氨酸NMDA受体激活将导致视网膜神经细胞的损伤⁸⁰。 动物模型研究的结果表明美金刚可以防止视网膜细胞的损伤⁸¹。

与安慰剂比较，三期试验的结果不支持美金刚能对进展性青光眼患者带来受益⁸²。

谷氨酸盐神经毒性被认为是导致亨廷顿病神经变性的潜在因素⁸³。在一项2年、多中心研究中，研究了美金刚（每天剂量达30mg）治疗27名亨廷顿病患者的有效性⁸³。这项初步研究的结果表明美金刚可以延缓疾病的进展⁸³。

临床前研究证实谷氨酸盐的兴奋作用在帕金森病神经元细胞的死亡过程中起部分作用⁸⁴。另外，帕金森病动物模型表明谷氨酸盐拮抗剂具有抗运动不能效应⁸⁴。因此，谷氨酸盐拮抗剂，例如美金刚，已被作为治疗治疗帕金森病相关征候、以及延缓疾病进展的候选药^84,85。并且NMDA受体拮抗剂美金刚已被用于治疗帕金森病⁸⁶。

在一项12名原发性帕金森病患者参加的临床研究中，美金刚改善了帕金森病患者的症状 ― 这种效应独立于当前的多巴胺类药物的治疗作用⁸⁷。对于美金刚能否改善药物诱导的运动失调（这是帕金森病患者长期接受多巴胺类药物治疗的一个特征），报道的结果不一致^86,87。

有一些研究报道美金刚对痴呆伴帕金森病的患者也有效^86,88，已有一项研究启动以评价美金刚治疗帕金森病的效果。也有大量关于美金刚治疗路易体痴呆（DLB）的报导，表明美金刚的症状性效用是可变的^89-91。

最近的研究表明精神分裂症患者前扣带回磷脂代谢增加⁹²。这一结果提供了精神分裂症神经变性机制的支持性证据⁹²。

有一些美金刚治疗神经分裂症的报导^93,94，结果表明美金刚能给神经分裂症患者到来一些治疗受益。然而，最近的一项双盲、安慰剂对照的研究评价美金刚作为非典型性抗精神病药物辅助治疗精神分裂症的安全性及有效性的结果表明，在主要有效性指标:PANSS总分方面，美金刚组与安慰剂组之间无显著差异（研究MD-29）⁷⁹。

 

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