Abstract
In the brain, acetylcholine (ACh) is regarded as one of the major neurotransmitters. During the advancement of Alzheimer's disease (AD) cholinergic deficits occur and this can lead to extensive cognitive dysfunction and decline. Acetylcholinesterase (AChE) remains a highly feasible target for the symptomatic improvement of AD. Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AChE for myasthenia gravis had effectively proven that AChE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEIs) have been continued to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs which are under development and their respective mechanisms of actions.
Keywords: Acetylcholine, acetylcholinesterase inhibitors, tacrine, donepezil, galantamine, rivastigmine, Alzheimer’s disease.
[http://dx.doi.org/10.3389/fnagi.2018.00004] [PMID: 29441009]
[http://dx.doi.org/10.1212/WNL.0b013e31828726f5] [PMID: 23390181]
[http://dx.doi.org/10.1159/000481812] [PMID: 29887680]
[http://dx.doi.org/10.9734/INDJ/2016/26317]
[http://dx.doi.org/10.1007/s12035-018-1237-z] [PMID: 30032423]
[http://dx.doi.org/10.1111/psyg.12368] [PMID: 30221441]
[http://dx.doi.org/10.1016/0165-6147(91)90609-V] [PMID: 1763432]
[http://dx.doi.org/10.1016/0896-6273(91)90052-2] [PMID: 1673054]
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[http://dx.doi.org/10.3389/fnins.2018.00025] [PMID: 29440986]
[http://dx.doi.org/10.4172/2161-0460.1000245]
[http://dx.doi.org/10.4172/2155-9562.1000397]
[http://dx.doi.org/10.1155/2012/728983] [PMID: 22216416]
[http://dx.doi.org/10.1016/B978-1-4160-6231-8.10054-6]
[http://dx.doi.org/10.5772/intechopen.78252]
[http://dx.doi.org/10.1007/s12035-019-01660-3]
[http://dx.doi.org/10.1016/S1474-4422(11)70072-2] [PMID: 21775213]
[http://dx.doi.org/10.2174/1381612825666191011102444]
[http://dx.doi.org/10.1161/HYP.0000000000000053 ]
[http://dx.doi.org/10.1016/0197-4580(95)02063-2] [PMID: 8744409]
[http://dx.doi.org/10.1007/BF00294179] [PMID: 8059605]
[http://dx.doi.org/10.1101/cshperspect.a006189] [PMID: 22229116]
[http://dx.doi.org/10.2174/1567205013666151218150322] [PMID: 26679855]
[PMID: 20054780]
[http://dx.doi.org/10.21767/2171-6625.1000126]
[http://dx.doi.org/10.1007/s12035-018-1420-2] [PMID: 30414087]
[http://dx.doi.org/10.1007/BF00308809] [PMID: 1759558]
[http://dx.doi.org/10.1016/0304-3940(95)12083-G] [PMID: 8584267]
[http://dx.doi.org/10.1002/ana.410410106] [PMID: 9005861]
[http://dx.doi.org/10.1002/jcp.27588] [PMID: 30362531]
[http://dx.doi.org/10.1038/srep13993] [PMID: 26358557]
[http://dx.doi.org/10.1016/0166-2236(82)90165-5]
[http://dx.doi.org/10.1017/S003329170004407X] [PMID: 6104344]
[http://dx.doi.org/10.1136/bmj.2.6150.1457] [PMID: 719462]
[http://dx.doi.org/10.1007/BF00307630] [PMID: 1703383]
[http://dx.doi.org/10.1002/ana.410100203] [PMID: 7283399]
[http://dx.doi.org/10.1097/00005072-199808000-00001] [PMID: 9720487]
[http://dx.doi.org/10.1212/WNL.57.3.481] [PMID: 11502917]
[http://dx.doi.org/10.1001/archneur.61.2.252] [PMID: 14967774]
[http://dx.doi.org/10.1007/978-3-7091-6139-5_17]
[http://dx.doi.org/10.1358/dot.2003.39.1.740206] [PMID: 12669110]
[http://dx.doi.org/10.1001/jama.1994.03510370037029] [PMID: 8139083]
[http://dx.doi.org/10.1212/WNL.57.3.489] [PMID: 11502918]
[http://dx.doi.org/10.1212/WNL.54.12.2261] [PMID: 10881250]
[http://dx.doi.org/10.1002/14651858.CD001191.pub2]
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[http://dx.doi.org/10.1345/aph.18211] [PMID: 10332536]
[http://dx.doi.org/10.2165/00002512-200421010-00004] [PMID: 14715043]
[http://dx.doi.org/10.4103/0974-2700.44674] [PMID: 19561947]
[PMID: 12166542]
[http://dx.doi.org/10.1046/j.1365-2125.1999.00026.x] [PMID: 10583015]
[http://dx.doi.org/10.1016/j.scitotenv.2019.134836]
[http://dx.doi.org/10.1007/s00401-011-0849-4] [PMID: 21691765]
[http://dx.doi.org/10.1016/S0896-6273(00)80108-7] [PMID: 8608006]
[http://dx.doi.org/10.1016/S1074-5521(97)90303-3] [PMID: 9427660]
[http://dx.doi.org/10.1007/0-387-23226-5_15] [PMID: 15709485]
[http://dx.doi.org/10.2174/1567205054367928] [PMID: 15974895]
[http://dx.doi.org/10.3389/fnmol.2011.00019] [PMID: 21949501]
[http://dx.doi.org/10.1002/ana.410360506] [PMID: 7979218]
[http://dx.doi.org/10.1136/jnnp.66.2.137]
[http://dx.doi.org/10.1111/j.1471-4159.1984.tb02801.x] [PMID: 6142924]
[http://dx.doi.org/10.1023/A:1022869222652] [PMID: 12675140]
[http://dx.doi.org/10.1212/WNL.59.4.563] [PMID: 12196650]
[http://dx.doi.org/10.1017/S1041610203008676] [PMID: 12636181]
[PMID: 12139365]
[http://dx.doi.org/10.1007/s007020200089] [PMID: 12111443]
[http://dx.doi.org/10.2165/00003088-200241100-00003] [PMID: 12162759]
[http://dx.doi.org/10.1016/j.ejphar.2003.11.080] [PMID: 14751402]
[http://dx.doi.org/10.1159/000051227] [PMID: 10971047]
[http://dx.doi.org/10.1007/s002130050931] [PMID: 10326778]
[PMID: 12139368]
[http://dx.doi.org/10.1016/0301-0082(91)90002-I] [PMID: 1714613]
[http://dx.doi.org/10.1097/00002093-199806000-00007] [PMID: 9651138]
[PMID: 9579280]
[http://dx.doi.org/10.1159/000106863] [PMID: 8866685]
[http://dx.doi.org/10.1007/BF00315027] [PMID: 2340845]
[http://dx.doi.org/10.1111/j.1600-0447.1990.tb05345.x] [PMID: 2248087]
[http://dx.doi.org/10.2165/00003088-199528060-00003] [PMID: 7656503]
[http://dx.doi.org/10.2165/00002018-199819060-00004] [PMID: 9880090]
[http://dx.doi.org/10.2165/00002018-199716010-00005] [PMID: 9010644]
[http://dx.doi.org/10.1007/bf03259636]
[http://dx.doi.org/10.1001/jama.1994.03510370044030] [PMID: 8139084]
[http://dx.doi.org/10.2165/00002018-200326110-00006] [PMID: 12908850]
[http://dx.doi.org/10.5980/jpnjurol1989.91.556] [PMID: 10897581]
[http://dx.doi.org/10.1097/00042752-199901000-00007] [PMID: 10336050]
[http://dx.doi.org/10.1212/WNL.50.1.136] [PMID: 9443470]
[http://dx.doi.org/10.1159/000017126] [PMID: 10325453]
[http://dx.doi.org/10.1248/bpb.18.1145] [PMID: 8535413]
[http://dx.doi.org/10.1016/0006-2952(90)90495-7] [PMID: 2390104]
[http://dx.doi.org/10.2165/00023210-200115050-00004] [PMID: 11475943]
[http://dx.doi.org/10.2165/00002512-199710030-00007] [PMID: 9108896]
[http://dx.doi.org/10.1016/S0924-977X(97)00079-5] [PMID: 9452942]
[http://dx.doi.org/10.1345/aph.17150] [PMID: 9475825]
[http://dx.doi.org/10.1016/j.jalz.2011.11.005] [PMID: 23110864]
[http://dx.doi.org/10.1007/s11940-013-0261-6] [PMID: 24222315]
[http://dx.doi.org/10.1007/s10072-013-1290-3] [PMID: 23370896]
[http://dx.doi.org/10.2165/00023210-199707020-00001] [PMID: 23338128]
[http://dx.doi.org/10.1517/13543784.9.10.2393] [PMID: 11060814]
[http://dx.doi.org/10.1055/s-1999-13983] [PMID: 10232064]
[http://dx.doi.org/10.1358/dot.1997.33.4.425052]
[http://dx.doi.org/10.1358/dot.1997.33.4.425053]
[http://dx.doi.org/10.1111/j.1600-0404.1998.tb00645.x] [PMID: 9576639]
[http://dx.doi.org/10.2165/00002512-199813050-00005] [PMID: 9829166]
[http://dx.doi.org/10.1177/2042098617750555] [PMID: 29492246]
[http://dx.doi.org/10.4088/PCC.14r01654] [PMID: 25667813]
[http://dx.doi.org/10.1002/14651858.CD001191.pub3]
[http://dx.doi.org/10.2165/00023210-200418130-00001] [PMID: 15521788]
[http://dx.doi.org/10.1185/030079907X233403] [PMID: 17892635]
[http://dx.doi.org/10.1185/03007995.2010.493788] [PMID: 20569067]
[http://dx.doi.org/10.11622/smedj.2018076] [PMID: 29931376]
[http://dx.doi.org/10.1080/13607860500410011] [PMID: 16798630]
[http://dx.doi.org/10.3233/JAD-170672] [PMID: 29254093]
[http://dx.doi.org/10.1093/ijnp/pyu115] [PMID: 25548104]
[http://dx.doi.org/10.1007/s12640-013-9398-z] [PMID: 23657927]
[http://dx.doi.org/10.1016/j.phrs.2004.05.005] [PMID: 15519530]
[http://dx.doi.org/10.1097/JCP.0b013e3181da5406] [PMID: 20473058]
[http://dx.doi.org/10.1136/bmj.332.7535.195] [PMID: 16439382]
[PMID: 9339266]
[http://dx.doi.org/10.4088/PCC.v05n0602] [PMID: 15213795]
[http://dx.doi.org/10.1016/j.jalz.2017.02.005] [PMID: 28341540]
[http://dx.doi.org/10.1016/S0011-393X(03)00059-6] [PMID: 24944370]
[http://dx.doi.org/10.1097/WAD.0b013e3181f883b7] [PMID: 20921876]
[http://dx.doi.org/10.1016/S1474-4422(07)70195-3] [PMID: 17689146]
[http://dx.doi.org/10.1093/gerona/58.4.M331] [PMID: 12663697]
[http://dx.doi.org/10.1002/gps.4405] [PMID: 26680338]
[PMID: 19300586]
[http://dx.doi.org/10.1002/14651858.CD001190]
[http://dx.doi.org/10.1002/14651858.CD001747]
[http://dx.doi.org/10.1212/WNL.57.4.613] [PMID: 11524468]
[http://dx.doi.org/10.7556/JAOA.2005.105.3.145] [PMID: 15863734]
[http://dx.doi.org/10.1093/ijnp/pyx012] [PMID: 28201726]
[PMID: 18686744]
[http://dx.doi.org/10.2165/00002018-199819060-00004] [PMID: 9880090]
[PMID: 19724715]
[http://dx.doi.org/10.2165/00002018-199819060-00004] [PMID: 9880090]
[http://dx.doi.org/10.1016/j.drudis.2013.01.008] [PMID: 23340113]
[http://dx.doi.org/10.4155/fmc-2016-0103] [PMID: 27774814]
[http://dx.doi.org/10.1002/ardp.201300074] [PMID: 24203864]
[http://dx.doi.org/10.1124/mol.105.015206] [PMID: 16223958]
[http://dx.doi.org/10.1039/c0md00256a]
[http://dx.doi.org/10.1016/j.ejmech.2013.01.039] [PMID: 23454517]
[http://dx.doi.org/10.1007/s00044-014-0931-2]
[http://dx.doi.org/10.1186/1750-1326-5-45] [PMID: 21040568]
[http://dx.doi.org/10.1016/j.bmcl.2012.04.029] [PMID: 22633691]
[http://dx.doi.org/10.1016/j.bmc.2008.12.067] [PMID: 19162488]
[http://dx.doi.org/10.1021/jm200853t] [PMID: 22023459]
[http://dx.doi.org/10.1007/s00702-012-0948-y] [PMID: 23238976]
[http://dx.doi.org/10.1016/S0968-0896(98)00133-3] [PMID: 9839013]
[http://dx.doi.org/10.1016/j.ejmech.2008.04.018] [PMID: 18550228]
[http://dx.doi.org/10.2174/156720512800618044] [PMID: 22211487]
[http://dx.doi.org/10.1016/S0223-5234(01)01324-1] [PMID: 11858843]
[http://dx.doi.org/10.1016/S0968-0896(03)00452-8] [PMID: 13129577]
[http://dx.doi.org/10.2174/1567205054367829] [PMID: 15974893]
[http://dx.doi.org/10.1021/jm049782n] [PMID: 15537349]