Mitic_2021_Expert.Opin.Drug.Metab.Toxicol__

INTRODUCTION: Alzheimer's disease and depression are health conditions affecting millions of people around the world. Both are strongly related to the level of the neurotransmitter acetylcholine. Since cholinergic deficit is characteristic of Alzheimer's disease, acetylcholinesterase inhibitors are applied as relevant drugs for the treatment of this disease, elevating the level of acetylcholine. On the other hand, a high level of acetylcholine is found to be associated with the symptoms of clinical depression. AREAS COVERED: This article aims to discuss if acetylcholinesterase inhibitors used as anti-Alzheimer's drugs could be the cause of the symptoms of clinical depression often linked to this neurological disorder. Emphasis will be put on drugs currently in use and on newly investigated natural products, which can inhibit AChE activity. EXPERT OPINION: Currently, it is not proven that the patient treated for Alzheimer's disease is prone to increased risk for depression due to the acetylcholinesterase inhibition, but there are strong indications. The level of acetylcholine is not the only factor in highly complicated diseases like AD and depression. Still, it needs to be considered isolated, keeping in mind the nature of presently available therapy, especially during a rational drug design process.