Rationale for combining glutamatergic and cholinergic approaches in the symptomatic treatment of Alzheimer’s disease

Abstract

A total of 40 years of biochemical, clinical and neuropathological research have revolutionized our understanding of the pathophysiology of Alzheimer’s disease, yet at the present moment the only drugs licensed for treatment are targeted essentially at symptoms. Some disease-modifying drugs remain in clinical trials, but many that have used similar approaches have failed. It is therefore of considerable interest to examine the optimal way of using existing medications for the benefit of patients. This article looks at the rationale behind the combined use of acetylcholinesterase inhibitors and the N-methyl-d-aspartate-receptor antagonist, memantine, from both preclinical and clinical perspectives.

Keywords::

• acetylcholine
• acetylcholinesterase inhibitor
• Alzheimer’s disease
• donepezil
• galantamine
• glutamate
• memantine
• N-methyl-d-aspartate-receptor
• rivastigmine

Financial and competing interest disclosure

PT Francis has received speaker bureau honoraria and grant support from H. Lundbeck A/S; speaker bureau honoraria from Novartis and Eisai; and has provided expert testimony to the UK High Court in a patent challenge against Novartis. CG Parsons is an employee of Merz Pharmaceuticals GmbH. RW Jones has received speaker bureau honoraria and/or consultancy fees from H Lundbeck A/S, Merz, Pfizer, Eisai and Novartis, as well as other companies involved in the development of new compounds for the treatment of Alzheimer’s disease and other dementias. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. The authors gratefully acknowledge the editorial support provided by Cambridge Medical Communication Limited, funded by H. Lundbeck A/S.