19982-08-2 Usage
Description
Memantine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor, which is a primary aliphatic amine that is the 3,5-dimethyl derivative of 1-aminoadamantane. It is a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist that binds preferentially to the NMDA receptor-operated cation channels. Memantine has been found to inhibit and reverse the abnormal activity of a protein phosphatase (PP-2A) that leads to tau hyperphosphorylation and neurofibrillary degeneration in Alzheimer's disease (AD).
Uses
1. Used in Alzheimer's Disease Treatment:
Memantine is used as a therapeutic agent for the treatment of both mild and moderate-to-severe Alzheimer's disease, as well as possibly vascular dementia (multi-infarct dementia). Its method of action involves acting as an uncompetitive, low-affinity, open-channel blocker, entering the receptor-associated ion channel preferentially when it is excessively open. Importantly, its off-rate is relatively fast, preventing substantial accumulation in the channel and thus not interfering with normal synaptic transmission.
2. Used in Vascular Dementia (VaD) Treatment:
Memantine has been used in patients with VaD based on its experimental efficacy in animal models of ischemic lesions. It acts on potentially contributing factors such as neuronal depolarization, mitochondrial dysfunction, magnesium effects on NMDA receptors, and chronic glutamatergic overstimulation. Additionally, Memantine has shown positive effects on long-term potentiation and cognitive tests in standard animal models of impaired synaptic plasticity.
3. Used in Antiulcer Treatment:
Memantine is also used in the treatment of antiulcer, although the specific application reason is not detailed in the provided materials.
Originator
Akatinol,Merz,W. Germany,1983
Manufacturing Process
A mixture of 24 g of 1,3-dimethyladamantane and 80 ml of bromine was refluxed for 6 hours. The reaction product mixture was cooled, taken up in about 200 ml of chloroform, and poured onto ice. The excess bromine was removed by adding sodium hydrosulfite. The chloroform layer was separated from the aqueous layer, dried, concentrated in vacuo, and distilled at reduced pressure to yield 30.5 g of product having a boiling point of about 118°C at 5- 6 mm; nD25 = 1.5169-1.5182. The product was identified by nuclear magnetic resonance (NMR) and elemental analyses as 1-bromo-3,5- dimethyladamantane.A mixture of 20 g of 1-bromo-3,5-dimethyladamantane, 75 ml of acetonitrile,
and 150 ml of concentrated sulfuric acid was allowed to react overnight at
ambient room temperature. The red reaction product mixture was poured over
crushed ice, and the white solid which precipitated was taken up in benzene
and the benzene solution dried over sodium hydroxide pellets. The benzene
solution was filtered from the drying agent and evaporated to dryness in
vacuo to yield 18.2 g of product having a melting point of about 97°C and
identified by infrared spectrum as 1-scetamido-3,5-dimethyladamantane.A mixture of 18 g of 1-acetamido-3,5-dimethyladamantane, 38 g of sodium
hydroxide, and 300 ml of diethylene glycol was refluxed for a period of 6
hours. The reaction product mixture was cooled and poured onto about 2,000
ml of crushed ice. The basic solution thus obtained was extracted five times
with 250 ml portions of benzene and the aqueous layer was discarded. The
combined benzene extracts were dried over sodium hydroxide and the dried
benzene solution concentrated in vacuo to give a crude oil weighing 14 g and
having nD25 = 1.4941, A 4 g sample of the crude oil was dissolved in ether
and the solution saturated with anhydrous hydrogen chloride. The solid which
precipitated was filtered off and recrystallized from a mixture of alcohol and
ether to yield product weighing 3.5 g and melting at 258°C.It was identified by analysis as 1-amino-3,5-dimethyladamantane
hydrochloride.
Therapeutic Function
Spasmolytic
Biological Activity
An antagonist at the NMDA receptor, binding to the ion channel site. Used in the treatment of Parkinsonism.
Clinical Use
NMDA-receptor antagonist:
Treatment of moderate to severe dementia in
Alzheimer’s disease
Metabolism
Molecular weight (daltons) 215.8
% Protein binding 45
% Excreted unchanged in urine 48 (74% plus
metabolites)
Volume of distribution (L/kg) 10
Half-life - normal/ESRF (hrs) 60-100 / 117-1561
Check Digit Verification of cas no
The CAS Registry Mumber 19982-08-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,9,9,8 and 2 respectively; the second part has 2 digits, 0 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 19982-08:
(7*1)+(6*9)+(5*9)+(4*8)+(3*2)+(2*0)+(1*8)=152
152 % 10 = 2
So 19982-08-2 is a valid CAS Registry Number.
InChI:InChI=1/C12H21N.ClH/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10;/h9H,3-8,13H2,1-2H3;1H/t9-,10+,11-,12-;
19982-08-2Relevant articles and documents
Kovacic,Roskos
, p. 5833 (1968)
-
Sasaki,T. et al.
, p. 3741 - 3743 (1977)
-
Green preparation method of memantine
-
Paragraph 0047-0056, (2021/09/15)
The method comprises the following steps: (1) mixing 1 - chlorine -3 and 5 - dimethyl adamantane with acetamide to obtain 1 -acetylamino -3 and 5 -dimethyladamantane. (2) The 1 -acetylamino -3, 5 -dimethyladamantane was deacetylated in a hot-water system to obtain a memantine. The preparation method provided by the invention is simple to operate. The method is safe, environment-friendly, high in yield and purity, cost-saving, low in production cost and beneficial to industrial production.
Memantine hydrochloride synthesis method
-
Paragraph 0061; 0067-0070; 0074; 0080-0084' 0088; 0094-0098, (2020/03/09)
The invention provides a memantine hydrochloride synthesis method, and belongs to the technical field of medicine synthesis. The preparation method comprises the following steps: carrying out a substitution reaction on 1-bromo-3,5-dimethyladamantane and acetamide to obtain 1-acetamido-3,5-dimethyladamantane, mixing the 1-acetamido-3,5-dimethyladamantane, an alcohol and an alkali, carrying out an alcoholysis reaction to obtain 1-amino-3,5-dimethyladamantane, and finally carrying out an acidification reaction on the 1-amino-3,5-dimethyladamantane and hydrochloric acid to obtain memantine hydrochloride. According to the method of the invention, 1-bromo-3,5-dimethyl adamantane and acetamide are used as the starting raw materials, so the sources of the raw materials are wide, the use of acetonitrile is avoided, and no pollution is caused to the human body and the environment; the use of catalysts is avoided in the whole reaction process, the reaction product is easy to separate, and the yield of the obtained memantine hydrochloride is high; and the method is mild in reaction condition and suitable for industrial production.
