Who invented Axura®?
Originally memantine was developed and marketed by Merz Pharmaceuticals GmbH, Germany, for the treatment of cognitive dysfunction. In 1991, Merz started a development program in the indication of dementia. The mechanism of action was elucidated by Merz scientists in their own research facilities.
What is the active ingredient of Axura® and how does it work?
Each tablet contains 10 mg of memantine hydrochloride (equivalent to 8.31 mg memantine). Memantine is a voltage-dependent, moderate affinity, uncompetitive NMDA-receptor antagonist. Memantine blocks pathological activation of NMDA receptors by excessive glutamate while preserving physiological function.
How can Axura® improve dementia symptoms while inhibiting the NMDA receptor?
Malfunctioning of glutamatergic neurotransmission, in particular at NMDA receptors, contributes to both expression of symptoms and disease progression in neurodegenerative dementia. Axura® is a moderate affinity, uncompetitive NMDA receptor antagonist. Due to the fast receptor kinetics and a pronounced voltage dependency, Axura® acts as a modulator of glutamatergic neurotransmission. On the one hand, under conditions of increased excitation by glutamate the NMDA receptor channel will be blocked. Thus, the neurons will be protected from the toxic effect of a long-term increased influx of calcium ions. On the other hand, at therapeutic concentrations, physiological neurotransmission will remain intact or be restored, thus improving the dementia symptoms.
What is the difference in the mechanism of action between Axura® and the cholinergic AD drugs approved so far?
Current drug therapies for Alzheimer's disease include cholinesterase inhibitors such as tacrine, donepezil, rivastigmine and galantamine. All of these drugs increase cholinergic synaptic transmission by inhibiting acetylcholinesterase at the synaptic cleft, thus increasing the concentration of acetylcholine. In contrast, Axura® acts via a completely different mechanism of action. Via NMDA receptor blockade Axura® protects the postsynaptic neuron against calcium overflow induced by excessive glutamate during pathological conditions. It is approved for moderate to severe Alzheimer’s disease. As opposed to Axura®, cholinergic AD drugs are only licensed for the treatment of mild to moderate Alzheimer's dementia.
Does Axura® have a neuroprotective effect?
Preclinical data clearly indicate that memantine might be able to slow down the progression of chronic neurodegenerative diseases. Memantine was shown to have a neuroprotective effect in acute and chronic experiments in vivo and in vitro.1 For example, in organotypic hippocampal cultures memantine protected from NMDA-induced neurotoxicity while normal neurotransmission remained intact2. In vivo, neuronal damage evoked by NMDA, the mitochondrial toxin 3-NP, lipopolysaccharide, and ?-amyloid was inhibited by memantine3.
Are there studies that show an inhibition of disease progression?
As elaborated above, the mechanism of action as well as the results of in vivo and in vitro experiments suggest that memantine has a neuroprotective effect. One can therefore assume that the progression of disease will also be inhibited. No studies have been designed so far to investigate a putative neuroprotective effect of memantine in man.
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