Memantine

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of memantine
General
Non-proprietary name Memantine
other names

3,5-dimethyltricyclo [3.3.1.1 3,7 ] decanamine ( IUPAC )

Molecular formula
  • C 12 H 21 N (memantine)
  • C 12 H 21 N HCl (memantine hydrochloride )
External identifiers / databases
CAS number
  • 19982-08-2 (memantine)
  • 41100-52-1 (memantine hydrochloride)
PubChem 4054
DrugBank DB01043
Wikidata Q412189
Drug information
ATC code

N06 DX01

Drug class

Anti-dementia

properties
Molar mass
  • 179.31 g · mol -1 (memantine)
  • 215.76 g · mol -1 (· memantine hydrochloride)
Physical state

firmly

Melting point

258 ° C or 290–295 ° C (memantine hydrochloride)

solubility

soluble in water (memantine hydrochloride )

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances

Hydrochloride

no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Memantine is a derivative of amantadine and is used to treat moderate to severe forms of dementia of the Alzheimer's disease . It is the only representative of the class of NMDA receptor antagonists (NMDA = N -methyl- D -aspartate) in anti-Alzheimer's drugs. However, its effectiveness is controversial.

Clinical information

Application areas (indications)

Memantine is approved in Europe and the USA for the treatment of moderate to severe Alzheimer's disease. In addition, it is used in Parkinson therapy as a drug in early therapy, just like amantadine itself. It is increasingly used in psychiatric disorders, where there is positive evidence of effectiveness in obsessive-compulsive disorder and ADHD .

Drug interactions

Memantine enhances the effects of anticholinergics and dopamine agonists . The effect of neuroleptics and barbiturates can be weakened. A therapy together with the cholinesterase inhibitor donepezil showed synergistic effects in studies.

unwanted effects

Side effects are motor restlessness, headache, tiredness, confusion, hallucinations , constipation, abnormal gait, dizziness , nausea , vomiting , increased tendency to convulsively.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Memantine is a moderately affine, non-competitive antagonist of the NMDA receptor and thus attacks the glutamatergic system. Glutamate is an excitatory neurotransmitter in the central nervous system and disorders in the glutamatergic neurotransmitter system play an important role in the pathophysiology of primary dementias .

Due to its specific binding behavior to the NMDA receptor, memantine blocks the harmful effects of glutamate, which lead to functional impairments and ultimately to the death of nerve cells . Memantine releases the ion channel connected to the receptor again as soon as a physiological signal is received, such as e.g. B. in cognitive processes. The learning and memory process can continue.

history

Memantine was developed by Merz and has been approved for the treatment of Alzheimer's disease since 2002. Memantine has been licensed by Forest for the USA and by Lundbeck for some European and international markets. Previously, memantine was used under the name Akatinol for the treatment of spastic disorders , organic brain syndrome , Parkinson's disease and mild and moderate brain disorders. The renaming and the extension of the indication went hand in hand with a considerable price increase.

Studies

Various studies have shown that the cholinergic deficit is not solely responsible for the dementia pathology, but that disorders in the glutamatergic neurotransmitter system play a decisive role in the pathology of dementia. That is why the modulation of the glutamate effect in the brain, which occurs primarily via NMDA receptors, is a new treatment approach.

In the case of moderate to severe Alzheimer's symptoms in the three core domains ( cognition , everyday skills , overall clinical impression), memantine therapy leads to statistically significant, but overall slight improvements or delays in symptoms after six months compared with placebo treatment. Furthermore, according to an evaluation of two randomized studies with the participation of the manufacturer Merz, treatment with this antidementia drug can help to reduce dementia-related behavioral disorders.

In 2009, the German Institute for Quality and Efficiency in Health Care examined all publicly accessible studies and the study data provided by the manufacturer as part of a drug evaluation and came to the conclusion that there was no evidence of a benefit of memantine therapy in patients with Alzheimer's disease give. In the areas of “activities of daily living” and “cognitive performance”, effects of memantine therapy would show up. However, due to the low level of these effects, their relevance is questionable, so that a benefit of the memantine treatment cannot be derived from them.

Based on the responder analyzes subsequently calculated by the Merz company and transmitted to the G-BA, the conclusion of the final report has changed as follows: Alzheimer's dementia. In the area of ​​everyday practical skills, if the uncertain response criteria and the simultaneously small size of the effect are observed, there is an indication of a benefit from memantine. "

Manufacturing

The synthesis from 1,3-dimethyl adamantane is described.

Trade names

Monopreparations

Memando (D), Axura (D, A, CH), Ebixa (D, A, CH)

Web links

Commons : Memantine  - collection of pictures, videos and audio files

Individual evidence

  1. ^ A b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA 2006, ISBN 0-911910-00-X , p. 1007.
  2. ↑ a b Datasheet Memantine hydrochloride from Sigma-Aldrich , accessed on June 15, 2011 ( PDF ).
  3. ↑ Joint statement on memantine of the German Society for Neurology and the German Society for Psychiatry, Psychotherapy and Neurology of October 27, 2010 (PDF file, 225KB) .
  4. ↑ Klaus Aktories, Ulrich Förstermann, Franz Hofmann, Klaus Starke: General and special pharmacology and toxicology . 10th edition. Elsevier, Urban & Fischer, Munich / Jena 2009, ISBN 978-3-437-42522-6 .
  5. ↑ M. Haghighi, L. Jahangard, H. Mohammad-Beigi: In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD) . In: Psychopharmacology . tape 228 , no. 4 , August 2013, p. 633-640 , doi : 10.1007 / s00213-013-3067-z , PMID 23525525 (English).
  6. ↑ Martin Winkler: Memantine as a new drug for ADD / HKS? Web4Health.info, March 12, 2007. Retrieved September 23, 2013.
  7. ↑ CB Surman, PG Hammerness, C. Petty, T. Spencer, R. Doyle, S. Napolean, N. Chu, D. Yorks, J. Biederman: A pilot open label prospective study of memantine monotherapy in adults with ADHD. In: The world journal of biological psychiatry: the official journal of the World Federation of Societies of Biological Psychiatry. Volume 14, number 4, May 2013, pp. 291-298, doi: 10.3109 / 15622975.2011.623716 . PMID 22436083 .
  8. ↑ PN Tariot include: Memantine Treatment in Patients With Moderate to Severe Alzheimer Disease Already Receiving Donepezil: A Randomized Controlled Trial. In: J. Am. Med. Assoc. Volume 291, No. 3, 2004, pp. 317-324. PMID 14734594 doi: 10.1001 / jama.291.3.317 .
  9. ^ Joint Formulary Committee (2004). British National Formulary (BNF) (47 ed.). London: British Medical Association and the Royal Pharmaceutical Society of Great Britain, ISBN 0-85369-584-9 .
  10. ↑ J. Kornhuber, J. Bormann, W. Retz, M. Hübers, P. Riederer: Memantine displaces [3H] MK-801 at therapeutic concentrations in postmortem human frontal cortex. In: Eur. J. Pharmacol. 166, 1989, pp. 589-590. PMID 2680528
  11. ↑ a b Rededicated: Memantine (Axura, Ebixa). In: Medicinal Telegram. Vol. 33, No. 9, 2002, p. 91. PDF (103 kB) .
  12. ^ T. Kaiser: Is the Axura price adjusted to the added value? In: Medicinal Telegram. Vol. 33; No. 8, 2002, p. 86. PDF (108 kB) .
  13. ↑ JT Greenamyre, AB Young: Excitatory amino acids and Alzheimer's disease. In: Neurobiol Aging. Volume 10, No. 5, 1989, pp. 593-602. doi: 10.1016 / 0197-4580 (89) 90143-7 .
  14. ^ R. McShane, A. Areosa Sastre, N. Minakaran: Memantine for dementia (Cochrane Review). In: The Cochrane Database of Systematic Reviews. No. 2, 2006, Art. No .: CD003154. doi: 10.1002 / 14651858.CD003154 .
  15. ↑ Gauthier et al .: Effects of memantine on behavioral symptoms in Alzheimer's disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data o two randomized, controlled studies. In: Int J Geriatr Psychiatry. No. 20, 2005, pp. 459-464. doi: 10.1002 / gps.1341 .
  16. ^ Institute for Quality and Efficiency in Health Care: Short version of the report "Memantine in Alzheimer's Dementia ". Published on September 10, 2009 (PDF)
  17. ↑ Institute for Quality and Efficiency in Health Care: Rapid Report A10-06 "Responder analyzes on memantine in Alzheimer's dementia", published on March 28, 2011. (PDF)
  18. ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher, Dietmar Reichert: Pharmaceutical Substances. 4th edition. 2 volumes. Thieme-Verlag, Stuttgart 2000, ISBN 1-58890-031-2 ; online since 2003 with biannual additions and updates.