1. Introduction 2. Cholinergic nervous system 3. Acetylcholinesterase structure and inhibitors action 4. Toxins inhibiting acetylcholinesterase 5. Alzheimer’s disease pathology 6. Inhibitors of AChE in current Alzheimer’s disease therapy 7. Trends in inhibitors for Alzheimer’s disease therapy 8. Current patents on the drugs for Alzheimer’s disease and related disorders 9. Drugs for myasthenia gravis 10. Expert opinion Review Acetylcholinesterase inhibitors: a patent review (2008 -- present) Miroslav Pohanka University of Defense, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic Introduction: Both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are present in the body in large amounts. AChE is an important part of the cholinergic nervous system taking place in the central and peripheral nervous system. AChE is a target of several toxins such as insecticide carbo- furan, nerve agents, sarin, soman, tabun and VX. Beside toxins, drugs for treatment of Alzheimer’s disease and myasthenia gravis, such as galantamine, donepezil, rivastigmine, tacrine, huperzine, pyridostigmine and neostigmine, are known. Areas covered: The review gives an overview of the importance of the cholin- ergic nervous system, the biochemistry of AChE and the role of AChE inhibi- tors. Current efforts to introduce potent drugs for Alzheimer’s disease therapy and reduce toxicity, while keeping the maximal pharmacological effect, are also discussed. Expert opinion: The current research effort into AChE inhibitors can be divided into two categories. First, new toxins useful for agricultural purposes and second, novel drugs that need to be prepared, although there is less interest in the new toxins. The research for drugs for Alzheimer’s disease needs to focus on inhibitors that reduce the deposition of amyloid plaques, but do not initiate AChE expression. Keywords: Alzheimer’s disease, carbofuran, donepezil, galantamine, huperzine, myasthenia gravis, nerve agents, pyridostigmine, rivastigmine, tacrine Expert Opin. Ther. Patents [Early Online] 1. Introduction Two enzymes rated among choliensterases are known. Both acetylcholinesterase (AChE; EC 3.1.1.7.) and butyrylcholinesterase (BChE; EC 3.1.1.8.) are presented in humans. AChE is expressed in multiple cells. It is present even on erythrocytes surface. However, the majority of AChE activity is present in cholinergic nervous system where it terminates cholinergic neurotransmission via fast hydrolysis of neurotransmitter acetylcholine [1]. Due to presence of AChE on erythrocytes, it was formerly called as a blood cholinesterase in some sources. Compared with AChE, BChE is not expressed in situ whereas it is produced by livers and distributed through plasma into the body. For the reason, BChE was in some sources called plasmatic, serum cholinesterase or pseudocholinesterase [2,3]. The both enzymes are markers of different pathologies including poisoning with cholinesterases inhibitors for the both cholinesterases and liver parenchyma degradation for BChE [4]. AChE is an object of interest in pharmacological and toxicological research [3]. The actual research is aimed at preparation of new pesticides effective to poison pest but harmless to humans. Synthesis of drugs useable for treatment of Alzheimer’s disease and myasthenia gravis is an interest of the current pharmaco- logical research. This review is focused on summarization of basic facts about AChE inhibitors, mechanism of their action and expectation in the next investiga- tion. Special attention is given to molecular mechanism of inhibitors action and link between AChE inhibition and alteration of the diseases. 10.1517/13543776.2012.701620 © 2012 Informa UK, Ltd. ISSN 1354-3776 1 All rights reserved: reproduction in whole or in part not permitted Expert Opin. Ther. Patents Downloaded from informahealthcare.com by University of Saskatchewan on 07/12/12 For personal use only.