They further indicate that the complex pharmacological profile of memantine requires careful consideration concerning suitable doses and suitable patient groups, so that the best use can be achieved for patients suffering from Alzheimer’s disease.
Dementia is an ever-increasing problem in today’s aging societies, with millions of patients and their carers affected worldwide. About one in five people over the age of 80 suffers from Alzheimer’s disease, the most common type of dementia. There is no cure and little hope is available for treatment, thus leaving the prospect of years or even decades of progressive mental deterioration.
In Alzheimer’s disease, two systems necessary for the communication of brain cells fail: The stimulatory brain messenger acetylcholine is down-regulated, while over-activation of the messenger glutamate leads to the death of neurones.
The first-generation of compounds aimed to boost the brain’s acetylcholine levels led to the development of drugs such as Aricept™ (donepezil) and Excelon™ (rivastigmine). Attempts to develop drugs that block the action of glutamate by a considerable number of pharmaceutical companies and researchers were not successful for a long time, since these receptors are also required for normal brain function, learning and memory in particular. It was therefore considered a major breakthrough when a drug called memantine was discovered to have beneficial effects in Alzheimer’s disease, which did not affect the normal function of glutamate signalling, but only the excessive actions leading to cell death. Memantine (trade names: Namenda™, Axura®, Ebixa®) was approved in 2002 by the European Agency for the Evaluation of Medicinal Products and in 2003 by the US FDA (Food and Drug Administration) for the treatment of moderate-to-severe Alzheimer’s disease. The arrival of this compound was greeted with great expectations since it could potentially be beneficial not only for Alzheimer’s disease, but also for other brain disorders that involve excess glutamate stimulation, such as trauma and stroke.
In the UK, much debate has centred on the recommendation of drugs which may help Alzheimer patients with day to day tasks. Cost-benefit analysis has led NICE (National Institute for Clinical Excellence (http://guidance.nice.org.uk/TA111/) to issue guidelines limiting the availability of Alzheimer-related drugs to specific patient groups. This decision has been widely criticized by patient representatives and Alzheimer support charities such as the Alzheimer’s Research Trust.
In the present study, researchers report that memantine has a much more complex pharmacological profile than originally described. It does in fact work rather similar to the originally introduced drugs that affect acetylcholine-related signalling, in addition to weak actions on glutamate, and has negative effects on neuronal communication at high concentrations. At lower concentrations, memantine was able to enhance signalling between neurones of the hippocampus (the main brain area affected in Alzheimer’s disease) and was indeed able to reverse learning and memory deficits. However, a pharmacological analysis showed that this was not due to its ability to block glutamate signalling, but rather to an additional and more potent action on the acetylcholine system.
Therefore, the investigators’ data do confirm that memantine shows promising aspects for the treatment of AD, but only in a narrow concentration range. More importantly, its complex pharmacological profile requires careful considerations concerning suitable doses and suitable patient groups, so that the best use can be achieved for patients suffering from Alzheimer’s disease.
Lead investigator Dr. Bettina Platt, University of Aberdeen, Institute of Medical Sciences, commented, “Clearly, the claim that memantine’s beneficial action is due to the reduction of glutamate signalling needs to be revised. It is highly unlikely that compounds directly targeting glutamate receptors will be successfully introduced into the clinic, since major side-effects must be expected.”
The article, "Memantine acts as a cholinergic stimulant in the mouse hippocampus" by Benjamin D. Drever, William G.L. Anderson, Helena Johnson, Matthew O’Callaghan, Sangwon Seo, Deog-Young Choi, Gernot Riedel, Bettina Platt, appears in the Journal of Alzheimer’s Disease, Volume 12, Issue 4 published by IOS Press.
Astrid Engelen | alfa
Statistical method developed at TU Dresden allows the detection of higher order dependencies
07.02.2020 | Technische Universität Dresden
Novel study underscores microbial individuality
13.12.2019 | Bigelow Laboratory for Ocean Sciences
Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.
The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...
Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics
Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...
Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.
A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...
The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.
Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
25.02.2020 | Power and Electrical Engineering
25.02.2020 | Earth Sciences
25.02.2020 | Life Sciences