What Are the Uses of Memantine Hydrochloride?

The chemical name of Memantine Hydrochloride is 3,5-Dimethyl-1-amino-adamantane hydrochloride, also known as 3,5-Dimethyl Tricyclo [3.3.1.1. (3.7)] decane-1-amino hydrochloride (3,5-Dimethyltricyclo (3.3.1.1 (3,7)) decan-1-amine hydrochloride). Its molecular formula is C12H21N · HCl.

Memantine hydrochloride is a drug for the treatment of dementia developed by the German company Merz. It is a new, low-to-medium affinity, voltage-dependent, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. It can block NMDA receptors non-competitively, reduce glutamate-induced over-excitation of NMDA receptors, prevent apoptosis, improve memory, and is a new generation of drugs that improve cognitive function. In February 2002, the European Patent and Drug Commission (CPMP) approved its use in the treatment of patients with moderate to severe Alzheimer's disease. It was launched in Germany in August of the same year, and was approved by the US Food and Drug Administration on October 17, 2003. (FDA) approved for the treatment of patients with moderate to severe Alzheimer's disease. Further research has shown that memantine hydrochloride is also effective in patients with mild to moderate Alzheimer's disease. Alzheimer disease (AD), also known as senile dementia, is one of the common diseases of the elderly, mainly manifested as memory loss and recognition dysfunction, etc., is a progressive neurodegenerative degenerative disease . Memantine hydrochloride is approved for the treatment of Alzheimer's disease.

As a chemical, memantine hydrochloride lacks some basic physical property data. According to some properties of amantadine, amantadine hydrochloride, and 1,3-dimethyladamantane, it can be inferred that memantine hydrochloride is soluble in organic solvents and slightly soluble in water. Low toxicity, no irritation to the skin, eyes, and mucous membranes, but as a medicine, it must be administered under the guidance of a doctor and must not be swallowed at will. ^[1-2]

Memantine hydrochloride physical properties

[Appearance] Memantine hydrochloride is white or off-white powder at room temperature.

[Melting point] (° C) 292

Memantine hydrochloride

[Density] 1

[Solubility] It can dissolve in organic solvents.

[Stability] stable

Memantine Hydrochloride Properties

[CAS registration number] 41100-52-1

[EINECS registration number] 255-219-6

[Molecular weight] 215.77

[Molecular formula and structural formula] The molecular formula is C ₁₂ H ₂₁ N · HCl. The chemical structural formula is as follows:

[Common chemical reactions] have some properties of amine salts.

[Incompatibility] Strong oxidant, strong alkali

[Polymerization Hazard] No Polymerization Hazard

Main uses of memantine hydrochloride

Memantine hydrochloride is a raw drug, and the tablet is called "Ebishen". This product should be prescribed by a doctor experienced in the diagnosis and treatment of Alzheimer's dementia and instruct patients to use it. Treatment can only be started if there is a caregiver who monitors the patient on time. Dementia should be diagnosed in accordance with current diagnostic criteria and guidelines.

Method for manufacturing memantine hydrochloride

Memantine hydrochloride has the following concentrated manufacturing methods:

(1) Grignard method: 1-bromo-3,5-dimethyladamantane is reacted with methyl lithium under ultrasonic conditions to obtain 1-lithium-3,5-dimethyladamantane. Then, it is reacted with NH4Cl to obtain memantine. Finally, it is acidified to form a salt, which is memantine hydrochloride.

(2) Acetonitrile method

1,3-dimethyladamantane is substituted with bromine to obtain 1-bromo-3,5-dimethyladamantane, and then acetamidinated to obtain 1-acetamido-3,5-dimethyladamantane . It is then hydrolyzed under alkaline conditions. Finally, it is acidified into a salt, which is memantine hydrochloride.
(3) Urea method 1,3-dimethyladamantane is brominated to obtain 1-bromo-3,5-dimethyladamantane. This intermediate reacts with urea to obtain N-3,5-dimethyl Memantine-1-based urea is hydrolyzed by ethylene glycol to obtain memantine, which is then acidified to form a salt, which is memantine hydrochloride.
The advantage of this method is that the raw material urea is easily available and the required reagents are less harmful to the environment, especially the intermediate products obtained by the amidation and alcoholysis reaction of 1-bromo-3,5-dimethyladamantane need not be separated and simplified The reaction steps. However, during the amidation reaction of 1-bromo-3,5-dimethyladamantane and urea, the steric hindrance is large, which results in a longer reaction time, a lower reaction yield, and higher industrial production costs. At the same time, during the alcoholysis process, the carbon atoms in the amide group of the urea compound have a poor activity to form C +, which leads to a decrease in the efficiency of the alcoholysis. Therefore, the required reaction temperature is high and the reaction conditions are harsh. The rate is only 31%, which is not suitable for large-scale production.
(4) Chlorination method uses anhydrous AlCl ₃ as a catalyst, and 1,3-dimethyladamantane is chlorinated to 1-chloro-3,5-dimethyladamantane through tert-butyl chloride, followed by acetamido It is converted into 1-acetamido-3,5-dimethyladamantane, then hydrolyzed to memantine, and then acidified to form a salt to obtain memantine hydrochloride. This method is suitable for industrial production, however, this method needs to be performed under anhydrous conditions, and AlCl ₃ is constantly added during the chlorination process. At the same time, t-butyl chloride itself is prone to elimination reactions and needs to be prepared on site, which is not easy to operate, and the chloride 1-chloro-3,5-dimethyladamantane itself is not high in activity, resulting in a low reaction conversion rate. During the entire reaction process, the reaction temperature is relatively strict and energy consumption is high.

(5) Nitrification method

Using N-hydroxyphthalimide (NHPI) as a catalyst, 1,3-dimethyladamantane is nitrated to obtain 1-nitro-3,5-dimethyladamantane. Then, it was reduced to memantine by Pd / C catalytic hydrogenation. Finally, the salt is acidified with hydrochloric acid to obtain memantine hydrochloride.
This method uses NHPI as a catalyst in the nitration reaction. The reaction conditions are mild, the conversion rate is high, bromine is not required, the equipment is not high, and the use of relatively toxic reagents is avoided. The intermediates do not need to be purified, and impurities can be eliminated. Removed at the end. However, this method has greater danger in catalytic hydrogenation, and the reduction time is longer (24h to 72h).

(6) Formamide method

The amidation reaction of 1,3-dimethyladamantane and formamide gives 1-formamido-3,5-dimethyladamantane, which is then acidified to form a salt, which is memantine hydrochloride. In this method, a large amount of NO ₂ gas is generated during the reaction, which causes a large amount of alkali to be used for neutralization in the post-treatment process.
(7) Direct amination 1,3-dimethyladamantane completes the bromine substitution reaction and Ritter reaction in one step under the action of bromine and acetonitrile. The intermediate product is directly alcoholized and hydrolyzed to memantine without isolation, and then acidified into a salt to obtain memantine hydrochloride. The raw material utilization rate of this method is not high, more by-products are generated, and it is not easy to separate and control.

[Industrial chain] 1,3-dimethyladamantane, memantine hydrochloride, Yibaishen

[Reference quality index]

Appearance: white crystal or powder

Melting range: 290 ° C-295 ° C

Loss on drying: 0.5%

Content: 98.5% (HPLC)

Memantine Hydrochloride Toxicity and Environmental Impact

Memantine hydrochloride is low-toxic and non-irritating to the skin and eyes. As a side effect of medicines, please refer to the instructions of the medicines. The harmful effects of the by-products and wastes on the environment and human life cannot be ignored.

Memantine hydrochloride packaging, storage and transportation

Memantine hydrochloride is packaged in an open cardboard or iron bucket lined with plastic film or kraft paper, and stored in a dry, ventilated, rain-proof and cool warehouse. Store separately from fortifiers, strong bases, and foods to prevent coexistence, transport, and storage.