中文药名：盐酸美金刚片

作用机理
据推测，兴奋性氨基酸谷氨酸能持久激活中枢神经系统N-甲基-D-天冬氨酸（NMDA）受体，有助于阿尔茨海默氏病的症状。美金刚胺被认为通过其作为低至中等亲和力的非竞争性（开放通道）NMDA受体拮抗剂的作用发挥其治疗作用，所述NMDA受体拮抗剂优先结合至NMDA受体操作的阳离子通道。没有证据表明美金刚可以预防或减缓阿尔茨海默氏病患者的神经变性。
适应症和用途
NAMENDA是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，可用于治疗中度至重度阿尔茨海默氏症型痴呆。
剂量和给药
•可以带或不带食物一起服用。
•初始剂量为每天5毫克。每天两次，以5mg的增量增加剂量至10mg的维持剂量。在增加剂量之前，应观察到至少用前一剂治疗一周。
•严重肾功能不全：建议剂量为每天两次两次，每次5 mg。
剂量形式和强度
•片剂：5mg 10mg  20mg
•口服溶液：2mg/mL
禁忌症
•NAMENDA禁用于对美金刚盐酸盐或制剂中使用的任何赋形剂过敏的患者。
警告和注意事项
•升高尿液pH值的条件可能会减少尿液中美金刚的消除，导致美金刚的血浆水平升高。
不良反应
最常见的不良反应（≥5％，大于安慰剂）是头晕，头痛，意识模糊和便秘。
包装供应/存储和处理方式
5mg片剂：
棕褐色的胶囊状薄膜衣片，一侧凹有“ 5”，另一侧凹有FL。
装满袋子的10粒/袋，NDC 55154-4617-0
10毫克片剂：
灰色的胶囊状薄膜衣片，一侧刻有“ 10”，另一侧刻有FL。
装满袋子的10片/袋，NDC 55154-4618-0
将Namenda片剂和口服溶液储存在25°C（77°F）； 允许在15-30°C（59-86°F）的范围内进行偏移[请参阅USP控制的室温]。 

中文药名：盐酸美金刚片

药品简介
新一代治疗老年性痴呆药品memantine hydrochloride（美国商品名Namenda欧洲商品名AXURA）获批准上市

阿尔茨海默氏病（Alzheimer’s disease，AD），又称老年性痴呆，是一种与衰老相关，以认知功能下降为特征的渐进性脑退行性疾病或综合症。病人整个大脑弥散性萎缩并出现明显的病理组织学改变——老年斑（senile plaque, SP）（或神经炎性斑，neuritic plaque）和神经原纤维缠结(neurofibrillary tangle, NFT)。病人认知功能下降并伴有神经元功能障碍、神经元数量减少、神经元体积扩大及突触缺失（I型营养障碍轴突）和胞内磷酸化tau（microtubule-associated protein tau）形成的成对螺旋丝，即NFT（II型营养障碍轴突）。此外，胞外的淀粉样蛋白（amyloid β-protein, Aβ）沉积形成SP，其周围环绕着营养障碍的突起。Aβ沉积形式由早期的弥散型聚集（不成熟的弥散斑）到形成成熟的致密斑，后者由直径为8nm的原纤维组成，用刚果红染色后在偏振光的照射下表现出双折射的特性。晚期的病理变化是由激活的小胶质细胞和星形胶质细胞参与的炎性反应所引起的，它们包围着沉积斑块。该病早期的行为学改变为轻微的记忆紊乱或个性改变，在5~10年内逐渐恶化，最终出现严重痴呆症状，生活不能自理。这种隐袭和破坏性的大脑退行性疾病剥夺了受害者最具人类特征的品质——记忆、推理、抽象化和语言的能力。 

一、临床症状 
AD几乎都是以不可觉察的方式开始发病，最初常常是偶然地、在回忆日常生活最近事件时遇到困难。病人可能无法回忆与某个人的交谈或参与过的某项活动，或者可能是对最近接受的某个项目的信息变得很迷惑，亦即以轻微认知障碍 (mild cognitive impairment，MCI)为先兆。患者往往是以纯粹的遗忘症状开始，其他认知方面很少或根本没有任何困难。MCI或早期AD患者完全保持清醒状态，没有明显的语言混乱，并保持着正常的运动和感觉功能。 
AD发病的最初几年，多数病人在一般认知功能方面即已出现一些问题，例如在时间感和空间感及进行正确自如的复杂操作方面屡屡出错，并出现用词和数学运算困难等。当这些轻微的差错变得逐渐引人注意时，病人可能对一些活动和爱好变得索然无趣、出现情感淡漠、情绪不稳定了。在渐进性的记忆和认知功能衰退后，许多病人开始经历第一次、然而是比较明显的运动功能障碍，包括手工操作、写作、绘画、正常行走等。在几年或十几年的病程中，AD会逐渐恶化到明显痴呆的地步。由于定向力完全丧失、记忆力严重缺损及认知功能障碍，许多病人活动受限，被迫常常坐着或躺着，最后可能死于某些小的呼吸系统疾病，如误吸或肺炎等。 

二、神经递质改变 
AD脑组织中发现的第一个神经递质异常是乙酰胆碱（Ach），合成和降解Ach的酶活性发生改变。因此，AD内侧隔核和基底前脑胆碱能神经元的数量与质量都发生变化。然而，在这些递质缺乏的同时，很快伴随着其他递质神经元的减少或丧失，包括谷氨酸（Glu）、γ-氨基丁酸（GABA）、生长抑素（SST）、促肾上腺皮质激素释放因子（CRF）和5-羟色胺（5-HT）等等。因此，AD神经递质缺乏是广泛性的，并且，还没有关于各种神经元亚型遭破坏过程的清晰线索。直到现在，只有胆碱能递质功能不足被真正用于AD治疗。 

**盐酸美金刚胺（memantine hydrochloride，，Namenda/Axura）——用于治疗中晚期阿尔茨海默氏病（老年性痴呆） 
多奈哌齐和重酒石酸卡巴拉汀具有副作用少，老年病人容易耐受的优点；盐酸美金刚胺是美国FDA批准用于治疗中晚期阿尔茨海默氏病（老年性痴呆）的唯一药物，它的作用机制独特，是第一个在阿尔茨海默氏病和血管性痴呆方面有显著疗效的NMDA拮抗剂，当谷氨酸以病理量释放时，美金刚胺可减少谷氨酸的神经毒性作用，当谷氨酸释放过少时，美金刚胺可以改善记忆过程所需谷氨酸的传递，临床研究表明美金刚胺用于老年痴呆症患者具有较好的耐受性，在精神病理学和行为测定中产生温和的有统计学意义的显著改善，有研究表明美金刚胺与其它药物联合使用可以增加疗效，但在没有确切适应症批准之前，我们不推荐联合用药；神经节苷脂（Ganglioside，简称GM）是一种复合糖脂，存在于哺乳动物细胞，特别是神经元细胞的胞膜中，是神经细胞膜的天然组成部分，神经节苷脂能从各方面影响神经膜的功能，改善阿尔茨海默氏病（老年性痴呆）患者记忆力。 

FAD日前批准/欧洲美金刚（美国商品名Namen  欧洲商品名AXURA）治疗中重度阿尔茨海默病，这也是第一个获ＦＤＡ批准可治疗较严重阿尔茨海默病的药物。美金刚为Ｎ－甲基－Ｄ－天门冬氨酸（ＮＭＤＡ）受体拮抗剂，可通过阻断谷氨酸盐的作用而缓解阿尔茨海默病患者的症状。该药物使用较为安全，最常见不良反应为眩晕（７％）、头痛（６％）和便秘（６％）。

Ebixa

Active Substance: memantine hydrochloride 
Common Name: memantine 
ATC Code: N06DX01
Marketing Authorisation Holder: H. Lundbeck A/S
Active Substance: memantine hydrochloride 
Status: Authorised
Authorisation Date: 2002-05-15
Therapeutic Area: Alzheimer Disease
Pharmacotherapeutic Group: Other antidementia drugs

Therapeutic Indication

Treatment of patients with moderate to severe Alzheimer's disease.

What is Ebixa?

Ebixa is a medicine that contains the active substance memantine hydrochloride. It is available as tablets (5 mg, 10 mg, 15 mg and 20 mg). Ebixa is also available as an oral solution, which is supplied with a pump that delivers 5 mg memantine hydrochloride with each activation.

What is Ebixa used for?

Ebixa is used to treat patients with moderate to severe Alzheimer’s disease. Alzheimer’s disease is a type of dementia (a brain disorder) that gradually affects memory, intellectual ability and behaviour.

The medicine can only be obtained with a prescription.

How is Ebixa used?

Treatment should be started and supervised by a doctor who has experience in the diagnosis and treatment of Alzheimer’s disease. Treatment should only be started if a caregiver is available who will regularly monitor the use of Ebixa by the patient.

Ebixa should be given once a day at the same time every day. To prevent side effects, the dose of Ebixa is gradually increased over the first three weeks of treatment: during the first week, the dose is 5 mg; in the second week, it is 10 mg; and during the third week, it is 15 mg. From week four onwards, the recommended maintenance dose is 20 mg once a day. The tolerance and dose should be assessed within three months after starting treatment, and from then on the benefits of continuing treatment with Ebixa should be re-assessed on a regular basis. The dose may need to be reduced in patients who have moderate or severe problems with their kidneys. If the solution is used, the dose should first be pumped onto a spoon or into a glass of water. It should not be poured or pumped directly into the mouth.

For more information, see the package leaflet.

How does Ebixa work?

The active substance in Ebixa, memantine hydrochloride, is an antidementia medicine. The cause of Alzheimer’s disease is unknown, but memory loss in the disease is believed to be due to a disturbance of message signals in the brain.

Memantine works by blocking special types of receptor called N-methyl-D-aspartate (NMDA) receptors, to which the neurotransmitter glutamate normally attaches. Neurotransmitters are chemicals in the nervous system that allow nerve cells to communicate with one another. Changes in the way glutamate transmits signals within the brain have been linked to the memory loss seen in Alzheimer’s disease. In addition, overstimulation of the NMDA receptors may result in cell damage or death. By blocking NMDA receptors, memantine improves the transmission of signals in the brain and reduces the symptoms of Alzheimer’s disease.

How has Ebixa been studied?

Ebixa has been studied in three main studies including a total of 1,125 patients with Alzheimer’s disease, some of whom had taken other medicines for their disease in the past.

The first study involved 252 patients with moderately severe to severe disease, while the other two involved a total of 873 patients with mild to moderate disease. Ebixa was compared with placebo (a dummy treatment) over 24 to 28 weeks. The main measures of effectiveness were the change in symptoms in three main areas: functional (the degree of disability), cognitive (the ability to think, learn and remember) and global (a combination of several areas including general function, cognitive symptoms, behaviour and the ability to carry out everyday activities).

Ebixa was also studied in three additional studies including a total of 1,186 patients with mild to severe disease.

What benefit has Ebixa shown during the studies?

Ebixa was more effective than placebo at controlling the symptoms of Alzheimer’s disease. In the study of moderately severe to severe disease, patients taking Ebixa had fewer symptoms than those taking placebo after 28 weeks, as measured on both global and functional scores. In the two studies of mild to moderate disease, patients on Ebixa had less severe symptoms after 24 weeks, as measured on the global and cognitive scores. However, when these results were considered along with those of the three additional studies, it was noted that the effect of Ebixa was smaller in patients with mild disease.

What is the risk associated with Ebixa?

The most common side effects with Ebixa (seen in between 1 and 10 patients in 100) are somnolence (sleepiness), dizziness, hypertension (high blood pressure), dyspnoea (difficulty breathing), constipation, headache and drug hypersensitivity (allergy to the medicine). For the full list of all side effects reported with Ebixa, see the package leaflet.

Ebixa should not be used in people who may be hypersensitive (allergic) to memantine hydrochloride or any of the other ingredients.

Why has Ebixa been approved?

The CHMP decided that Ebixa’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Other information about Ebixa

The European Commission granted a marketing authorisation valid throughout the European Union for Ebixa on 15 May 2002.

For more information about treatment with Ebixa, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.