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
Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung
High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences