MMSL 2018, 87(1):34-44 | DOI: 10.31482/mmsl.2018.006

PRO-COGNITIVE EFFECT OF BIS(7)-TACRINE AS POTENTIAL THERAPEUTIC AGENT AGAINST NEURODEGENERATIVE DISORDERSReview article

Jan Korábečný ORCID...1,2
1 Katedra toxikologie a vojenské farmacie, Fakulta vojenského zdravotnictví, Univerzita obrany, Třebešská 1575, 500 02, Hradec Králové, Česká republika
2 Centrum biomedicínského výzkumu, Fakultní nemocnice Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Česká republika

Na základě poznatků získaných z krystalografie acetylcholinesterasy (AChE) byly koncipovány nové homo- i heterodimerní molekuly, které jsou schopné vázat se do obou anionických míst enzymu a tím nejen zvýšit svůj inhibiční potenciál, ale i současně ovlivňovat další patologické mechanismy AD. Průkopnickou molekulou se v tomto ohledu stal bis(7)-takrin, který vznikl zdvojením takrinu přes alifatický můstek o délce sedmi uhlíkových atomů. Bis(7)-takrin je zajímavou multipotentní sloučeninou, která je schopna ovlivňovat řadu receptorových i enzymových systémů za podmínek in vitro i in vivo. Stal se rovněž předlohovou strukturou pro celou řadu nových sloučenin s dalšími pozitivními vlastnostmi, které jsou relevantní pro terapii AD.

Keywords: acetylcholinesterasa; Alzheimerova choroba; bis(7)-takrin; neurodegenerace; takrin

The acetylcholinesterase (AChE) structure elucidation has significantly contributed to the development of both novel homo- and heterodimer molecules that are capable of simultaneous binding to both anionic sites of the enzyme. This mostly resulted into improved AChE inhibition potency concurrently affecting other pathological hallmarks of the disease. In this regard, bis(7)-tacrine can be considered as the pioneering molecule. It consists of two tacrine moieties connected via alkylene tether of seven carbon atoms. In in vitro and in vivo, bis(7)-tacrine revealed interesting multipotent profile capable to affect several enzymes and receptors which are implicated in the pathogenesis of AD. It also became a key structural template in the development of other more potent compounds intended for the therapy of neurodegenerative disorders.

Keywords: acetylcholinesterase; Alzheimer’s disease; bis(7)-tacrine; neurodegeneration; tacrine

Received: February 1, 2018; Revised: February 8, 2018; Published: March 9, 2018  Show citation

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Korábečný, J. (2018). PRO-COGNITIVE EFFECT OF BIS(7)-TACRINE AS POTENTIAL THERAPEUTIC AGENT AGAINST NEURODEGENERATIVE DISORDERS. MMSL, 87(1), 34-44. doi: 10.31482/mmsl.2018.006
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    References

    1. Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, et al. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science. 23. srpen 1991;253(5022):872-9. Go to original source...
    2. Hofer P, Fringeli UP. Acetylcholinesterase kinetics. Biophys Struct Mech. 1981;8(1-2):45-59. Go to original source... Go to PubMed...
    3. Almasieh M, MacIntyre JN, Pouliot M, Casanova C, Vaucher E, Kelly MEM, et al. Acetylcholinesterase inhibition promotes retinal vasoprotection and increases ocular blood flow in experimental glaucoma. Invest Ophthalmol Vis Sci. 3. květen 2013;54(5):3171-83. Go to original source... Go to PubMed...
    4. Komloova M, Musilek K, Dolezal M, Gunn-Moore F, Kuca K. Structure-activity relationship of quaternary acetylcholinesterase inhibitors - outlook for early myasthenia gravis treatment. Curr Med Chem. 2010;17(17):1810-24. Go to original source...
    5. Nachmansohn D, Wilson IB. The enzymic hydrolysis and synthesis of acetylcholine. Adv Enzymol Relat Subj Biochem. 1951;12:259-339. Go to original source... Go to PubMed...
    6. Taylor P, Lappi S. Interaction of fluorescence probes with acetylcholinesterase. The site and specificity of propidium binding. Biochemistry (Mosc). 6. květen 1975;14(9):1989-97. Go to original source... Go to PubMed...
    7. Perry EK, Perry RH, Blessed G, Tomlinson BE. Changes in Brain Cholinesterases in Senile Dementia of Alzheimer Type. Neuropathol Appl Neurobiol. 1. červenec 1978;4(4):273-7. Go to original source...
    8. Bartus RT, Dean RL, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science. 30. červenec 1982;217(4558):408-14. Go to original source...
    9. Mohs RC, Davis BM, Johns CA, Mathe AA, Greenwald BS, Horvath TB, et al. Oral physostigmine treatment of patients with Alzheimer's disease. Am J Psychiatry. leden 1985;142(1):28-33. Go to original source... Go to PubMed...
    10. Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A. Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med. 13. listopad 1986;315(20):1241-5. Go to original source... Go to PubMed...
    11. Patocka J, Jun D, Kuca K. Possible role of hydroxylated metabolites of tacrine in drug toxicity and therapy of Alzheimer's disease. Curr Drug Metab. květen 2008;9(4):332-5. Go to original source... Go to PubMed...
    12. Balson R, Gibson PR, Ames D, Bhathal PS. Tacrine-Induced Hepatotoxicity. CNS Drugs. 1. zaři 1995;4(3):168-81. Go to original source...
    13. Spilovska K, Korabecny J, Sepsova V, Jun D, Hrabinova M, Jost P, et al. Novel Tacrine-Scutellarin Hybrids as Multipotent Anti-Alzheimer's Agents: Design, Synthesis and Biological Evaluation. Mol Basel Switz. 16. červen 2017;22(6).
    14. Nepovimova E, Korabecny J, Dolezal R, Babkova K, Ondrejicek A, Jun D, et al. Tacrine-Trolox Hybrids: A Novel Class of Centrally Active, Nonhepatotoxic Multi-Target-Directed Ligands Exerting Anticholinesterase and Antioxidant Activities with Low In Vivo Toxicity. J Med Chem. 25. listopad 2015;58(22):8985-9003. Go to original source... Go to PubMed...
    15. Spilovska K, Korabecny J, Horova A, Musilek K, Nepovimova E, Drtinova L, et al. Design, synthesis and in vitro testing of 7-methoxytacrine-amantadine analogues: a novel cholinesterase inhibitors for the treatment of Alzheimer's disease. Med Chem Res. 1. červen 2015;24(6):2645-55. Go to original source...
    16. Spilovska K, Korabecny J, Nepovimova E, Dolezal R, Mezeiova E, Soukup O, et al. Multitarget Tacrine Hybrids with Neuroprotective Properties to Confront Alzheimer's Disease. Curr Top Med Chem. 2017;17(9):1006-26. Go to original source... Go to PubMed...
    17. Prati F, Cavalli A, Bolognesi ML. Navigating the Chemical Space of Multitarget-Directed Ligands: From Hybrids to Fragments in Alzheimer's Disease. Mol Basel Switz. 8. duben 2016;21(4):466.
    18. Pang YP, Quiram P, Jelacic T, Hong F, Brimijoin S. Highly potent, selective, and low cost bistetrahydroaminacrine inhibitors of acetylcholinesterase. Steps toward novel drugs for treating Alzheimer's disease. J Biol Chem. 27. zaři 1996;271(39):23646-9. Go to original source... Go to PubMed...
    19. del Monte-Millan M, Garcia-Palomero E, Valenzuela R, Usan P, de Austria C, Munoz-Ruiz P, et al. Dual binding site acetylcholinesterase inhibitors: potential new disease-modifying agents for AD. J Mol Neurosci MN. 2006;30(1-2):85-8. Go to original source... Go to PubMed...
    20. Alvarez A, Opazo C, Alarcon R, Garrido J, Inestrosa NC. Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils. J Mol Biol. 26. zaři 1997;272(3):348-61. Go to original source... Go to PubMed...
    21. De Ferrari GV, Canales MA, Shin I, Weiner LM, Silman I, Inestrosa NC. A Structural Motif of Acetylcholinesterase That Promotes Amyloid β-Peptide Fibril Formation. Biochemistry (Mosc). 1. zaři 2001;40(35):10447-57. Go to original source... Go to PubMed...
    22. Dvir H, Silman I, Harel M, Rosenberry TL, Sussman JL. Acetylcholinesterase: From 3D Structure to Function. Chem Biol Interact. 6. zaři 2010;187(1-3):10-22. Go to original source... Go to PubMed...
    23. Carlier PR, Han YF, Chow ES, Li CP, Wang H, Lieu TX, et al. Evaluation of short-tether bis-THA AchE inhibitors. A further test of the dual binding site hypothesis. Bioorg Med Chem. unor 1999;7(2):351-7. Go to original source...
    24. Hu M-K, Wu L-J, Hsiao G, Yen M-H. Homodimeric Tacrine Congeners as Acetylcholinesterase Inhibitors. J Med Chem. 1. květen 2002;45(11):2277-82. Go to original source...
    25. Lee SK, Park MK, Jhang HE, Yi J, Nahm K, Cho DW, et al. Preparation of 7-Methoxy Tacrine Dimer Analogs and Their In vitro/In silico Evaluation as Potential Cholinesterase Inhibitors. Bull Korean Chem Soc. červen 2015;36(6):1654-60. Go to original source...
    26. Korabecny J, Holas O, Musilek K, Pohanka M, Opletalova V, Dohnal V, et al. Synthesis and In Vitro Evaluation of New Tacrine Derivates-Bis-Alkylene Linked 7-MEOTA. Lett Org Chem. 1. červen 2010;7(4):327-31. Go to original source...
    27. Rydberg EH, Brumshtein B, Greenblatt HM, Wong DM, Shaya D, Williams LD, et al. Complexes of alkylenelinked tacrine dimers with Torpedo californica acetylcholinesterase: Binding of Bis5-tacrine produces a dramatic rearrangement in the active-site gorge. J Med Chem. 7. zaři 2006;49(18):5491-500. Go to original source... Go to PubMed...
    28. Minarini A, Milelli A, Tumiatti V, Rosini M, Simoni E, Bolognesi ML, et al. Cystamine-tacrine dimer: a new multi-target-directed ligand as potential therapeutic agent for Alzheimer's disease treatment. Neuropharmacology. unor 2012;62(2):997-1003. Go to original source... Go to PubMed...
    29. Eslami M, Hashemianzadeh SM, Bagherzadeh K, Seyed Sajadi SA. Molecular perception of interactions between bis(7)tacrine and cystamine-tacrine dimer with cholinesterases as the promising proposed agents for the treatment of Alzheimer's disease. J Biomol Struct Dyn. 2016;34(4):855-69. Go to original source... Go to PubMed...
    30. Bolognesi ML, Cavalli A, Valgimigli L, Bartolini M, Rosini M, Andrisano V, et al. Multi-target-directed drug design strategy: from a dual binding site acetylcholinesterase inhibitor to a trifunctional compound against Alzheimer's disease. J Med Chem. 27. prosinec 2007;50(26):6446-9. Go to original source... Go to PubMed...
    31. Qian S, He L, Mak M, Han Y, Ho C-Y, Zuo Z. Synthesis, biological activity, and biopharmaceutical characterization of tacrine dimers as acetylcholinesterase inhibitors. Int J Pharm. 30. prosinec 2014;477(1-2):442-53. Go to original source... Go to PubMed...
    32. Bolognesi ML, Bartolini M, Mancini F, Chiriano G, Ceccarini L, Rosini M, et al. Bis(7)-tacrine derivatives as multitarget-directed ligands: Focus on anticholinesterase and antiamyloid activities. ChemMedChem. 2. srpen 2010;5(8):1215-20. Go to original source... Go to PubMed...
    33. Xiao XQ, Lee NT, Carlier PR, Pang Y, Han YF. Bis(7)-tacrine, a promising anti-Alzheimer's agent, reduces hydrogen peroxide-induced injury in rat pheochromocytoma cells: comparison with tacrine. Neurosci Lett. 1. zaři 2000;290(3):197-200. Go to original source...
    34. Li CY, Wang H, Xue H, Carlier PR, Hui KM, Pang YP, et al. Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist. Neuroreport. 17. březen 1999;10(4):795-800. Go to original source... Go to PubMed...
    35. Zhou L, Liu Y-W, Peoples RW, Yang M, Tian X, Ai Y-X, et al. Mechanism of bis(7)-tacrine inhibition of GABAactivated current in cultured rat hippocampal neurons. Neuropharmacology. červenec 2009;57(1):33-40. Go to original source... Go to PubMed...
    36. Moore H, Sarter M, Bruno JP. Age-dependent modulation of in vivo cortical acetylcholine release by benzodiazepine receptor ligands. Brain Res. 20. listopad 1992;596(1-2):17-29. Go to original source... Go to PubMed...
    37. Zhao Y, Li W, Chow PCY, Lau DTK, Lee NTK, Pang Y, et al. Bis(7)-tacrine, a promising anti-Alzheimer's dimer, affords dose- and time-dependent neuroprotection against transient focal cerebral ischemia. Neurosci Lett. 11. červenec 2008;439(2):160-4. Go to original source... Go to PubMed...
    38. Shu X-J, Liu W, Zhang L, Yang R, Yi H-L, Li C-L, et al. Effect of bis(7)-tacrine on cognition in rats with chronic cerebral ischemia. Neurosci Lett. 23. březen 2012;512(2):103-8. Go to original source... Go to PubMed...
    39. Li J, Lu Z, Xu L, Wang Q, Zhang Z, Fang J. Neuroprotective effects of bis(7)-tacrine in a rat model of pressureinduced retinal ischemia. Cell Biochem Biophys. březen 2014;68(2):275-82. Go to original source... Go to PubMed...
    40. Han Y-F, Wu D-C, Xiao X-Q, Chen PMY, Chung W, Lee NTK, et al. Protection against ischemic injury in primary cultured astrocytes of mouse cerebral cortex by bis(7)-tacrine, a novel anti-Alzheimer's agent. Neurosci Lett. 14. červenec 2000;288(2):95-8. Go to original source...
    41. Li C, Carlier PR, Ren H, Kan KKW, Hui K, Wang H, et al. Alkylene tether-length dependent gammaaminobutyric acid type A receptor competitive antagonism by tacrine dimers. Neuropharmacology. Unor 2007;52(2):436-43. Go to original source... Go to PubMed...
    42. Ros E, Aleu J, Gomez de Aranda I, Canti C, Pang YP, Marsal J, et al. Effects of bis(7)-tacrine on spontaneous synaptic activity and on the nicotinic ACh receptor of Torpedo electric organ. J Neurophysiol. červenec 2001;86(1):183-9. Go to original source... Go to PubMed...
    43. Luo J-L, Zhang J, Guan B-C, Pang Y-P, Han Y-F, Li Z-W. Inhibition by bis(7)-tacrine of 5-HT-activated current in rat TG neurons. Neuroreport. 7. červen 2004;15(8):1335-8. Go to original source... Go to PubMed...
    44. Hynd MR, Scott HL, Dodd PR. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease. Neurochem Int. řijen 2004;45(5):583-95. Go to original source... Go to PubMed...
    45. Zemek F, Drtinova L, Nepovimova E, Sepsova V, Korabecny J, Klimes J, et al. Outcomes of Alzheimer's disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin Drug Saf. červen 2014;13(6):759-74.
    46. Spilovska K, Zemek F, Korabecny J, Nepovimova E, Soukup O, Windisch M, et al. Adamantane - A Lead Structure for Drugs in Clinical Practice. Curr Med Chem. 2016;23(29):3245-66. Go to original source...
    47. Horak M, Holubova K, Nepovimova E, Krusek J, Kaniakova M, Korabecny J, et al. The pharmacology of tacrine at N-methyl-d-aspartate receptors. Prog Neuropsychopharmacol Biol Psychiatry. 3. duben 2017;75:54-62. Go to original source... Go to PubMed...
    48. Li W, Pi R, Chan HHN, Fu H, Lee NTK, Tsang HW, et al. Novel dimeric acetylcholinesterase inhibitor bis7-tacrine, but not donepezil, prevents glutamate-induced neuronal apoptosis by blocking N-methyl-D-aspartate receptors. J Biol Chem. 6. květen 2005;280(18):18179-88. Go to original source... Go to PubMed...
    49. Fu H, Li W, Liu Y, Lao Y, Liu W, Chen C, et al. Mitochondrial proteomic analysis and characterization of the intracellular mechanisms of bis(7)-tacrine in protecting against glutamate-induced excitotoxicity in primary cultured neurons. J Proteome Res. červenec 2007;6(7):2435-46. Go to original source... Go to PubMed...
    50. Liu Y-W, Luo J-L, Ren H, Peoples RW, Ai Y-X, Liu L-J, et al. Inhibition of NMDA-gated ion channels by bis(7)-tacrine: whole-cell and single-channel studies. Neuropharmacology. červen 2008;54(7):1086-94. Go to original source... Go to PubMed...
    51. Fang JH, Wang XH, Xu ZR, Jiang FG. Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage. BMC Neurosci. 3. březen 2010;11:31. Go to original source... Go to PubMed...
    52. Kawasaki H, Morooka T, Shimohama S, Kimura J, Hirano T, Gotoh Y, et al. Activation and involvement of p38 mitogen-activated protein kinase in glutamate-induced apoptosis in rat cerebellar granule cells. J Biol Chem. 25. červenec 1997;272(30):18518-21. Go to original source... Go to PubMed...
    53. Jiang Q, Gu Z, Zhang G, Jing G. Diphosphorylation and involvement of extracellular signal-regulated kinases (ERK1/2) in glutamate-induced apoptotic-like death in cultured rat cortical neurons. Brain Res. 28. unor 2000;857(1):71-7. Go to original source... Go to PubMed...
    54. Liu Y, Li C. Inhibition of N-methyl-D-aspartate-activated current by bis(7)-tacrine in HEK-293 cells expressing NR1/NR2A or NR1/NR2B receptors. J Huazhong Univ Sci Technol Med Sci Hua Zhong Ke Ji Xue Xue Bao Yi Xue Ying Wen Ban Huazhong Keji Daxue Xuebao Yixue Yingdewen Ban. prosinec 2012;32(6):793-7. Go to original source... Go to PubMed...
    55. Woodruff GN, Foster AC, Gill R, Kemp JA, Wong EH, Iversen LL. The interaction between MK-801 and receptors for N-methyl-D-aspartate: functional consequences. Neuropharmacology. červenec 1987;26(7B):903-9. Go to original source... Go to PubMed...
    56. Liu Y-W, Li C-Y, Luo J-L, Li W-M, Fu H-J, Lao Y-Z, et al. Bis(7)-tacrine prevents glutamate-induced excitotoxicity more potently than memantine by selectively inhibiting NMDA receptors. Biochem Biophys Res Commun. 16. květen 2008;369(4):1007-11. Go to original source... Go to PubMed...
    57. Luo J, Li W, Liu Y, Zhang W, Fu H, Lee NTK, et al. Novel dimeric bis(7)-tacrine proton-dependently inhibits NMDA-activated currents. Biochem Biophys Res Commun. 21. zaři 2007;361(2):505-9. Go to original source... Go to PubMed...
    58. Yamauchi M, Omote K, Ninomiya T. Direct evidence for the role of nitric oxide on the glutamate-induced neuronal death in cultured cortical neurons. Brain Res. 12. leden 1998;780(2):253-9. Go to original source...
    59. Keil U, Bonert A, Marques CA, Scherping I, Weyermann J, Strosznajder JB, et al. Amyloid beta-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis. J Biol Chem. 26. listopad 2004;279(48):50310-20. Go to original source... Go to PubMed...
    60. Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M. Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science. 11. červen 1999;284(5421):1845-8. Go to original source...
    61. Li W, Lee NTK, Fu H, Kan KKW, Pang Y, Li M, et al. Neuroprotection via inhibition of nitric oxide synthase by bis(7)-tacrine. Neuroreport. 3. duben 2006;17(5):471-4. Go to original source... Go to PubMed...
    62. Li W, Xue J, Niu C, Fu H, Lam CSC, Luo J, et al. Synergistic neuroprotection by bis(7)-tacrine via concurrent blockade of N-methyl-D-aspartate receptors and neuronal nitric-oxide synthase. Mol Pharmacol. květen 2007;71(5):1258-67. Go to original source... Go to PubMed...
    63. Fu H, Li W, Lao Y, Luo J, Lee NTK, Kan KKW, et al. Bis(7)-tacrine attenuates beta amyloid-induced neuronal apoptosis by regulating L-type calcium channels. J Neurochem. zaři 2006;98(5):1400-10. Go to original source... Go to PubMed...
    64. Ueda K, Shinohara S, Yagami T, Asakura K, Kawasaki K. Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals. J Neurochem. leden 1997;68(1):265-71. Go to original source... Go to PubMed...
    65. Nie H, Yu W-J, Li X-Y, Yuan C-H, Pang Y-P, Li C-Y, et al. Inhibition by bis(7)-tacrine of native delayed rectifier and KV1.2 encoded potassium channels. Neurosci Lett. 29. leden 2007;412(2):108-13. Go to original source... Go to PubMed...
    66. Yu SP. Regulation and critical role of potassium homeostasis in apoptosis. Prog Neurobiol. červenec 2003;70(4):363-86. Go to original source...
    67. Li X-Y, Zhang J, Dai J-P, Liu X-M, Li Z-W. Actions of bis(7)-tacrine and tacrine on transient potassium current in rat DRG neurons and potassium current mediated by K(V)4.2 expressed in Xenopus oocyte. Brain Res. 8. březen 2010;1318:23-32. Go to original source... Go to PubMed...
    68. Fu H, Li W, Luo J, Lee NTK, Li M, Tsim KWK, et al. Promising anti-Alzheimer's dimer bis(7)-tacrine reduces beta-amyloid generation by directly inhibiting BACE-1 activity. Biochem Biophys Res Commun. 15. unor 2008;366(3):631-6. Go to original source... Go to PubMed...
    69. Fu H, Dou J, Li W, Cui W, Mak S, Hu Q, et al. Promising multifunctional anti-Alzheimer's dimer bis(7)-Cognitin acting as an activator of protein kinase C regulates activities of α-secretase and BACE-1 concurrently. Eur J Pharmacol. 25. listopad 2009;623(1):14-21. Go to original source... Go to PubMed...
    70. Wang H, Carlier PR, Ho WL, Lee NT, Pang YP, Han YF. Attenuation of scopolamine-induced deficits in navigational memory performance in rats by bis(7)-tacrine, a novel dimeric AChE inhibitor. Zhongguo Yao Li Xue Bao. březen 1999;20(3):211-7.
    71. Bymaster FP, Heath I, Hendrix JC, Shannon HE. Comparative behavioral and neurochemical activities of cholinergic antagonists in rats. J Pharmacol Exp Ther. řijen 1993;267(1):16-24. Go to PubMed...
    72. Wang H, Carlier PR, Ho WL, Wu DC, Lee NT, Li CP, et al. Effects of bis(7)-tacrine, a novel anti-Alzheimer's agent, on rat brain AChE. Neuroreport. 17. březen 1999;10(4):789-93. Go to original source... Go to PubMed...
    73. Pan S-Y, Yu Z-L, Xiang C-J, Dong H, Fang H-Y, Ko K-M. Comparison studies of tacrine and bis7-tacrine on the suppression of scopolamine-induced behavioral changes and inhibition of acetylcholinesterase in mice. Pharmacology. 2009;83(5):294-300. Go to original source... Go to PubMed...
    74. Pan S-Y, Zhang Y, Guo B-F, Han Y-F, Ko K-M. Tacrine and bis(7)-tacrine attenuate cycloheximide-induced amnesia in mice, with attention to acute toxicity. Basic Clin Pharmacol Toxicol. řijen 2011;109(4):261-5. Go to original source... Go to PubMed...
    75. Fisher A, Mantione CR, Abraham DJ, Hanin I. Long-term central cholinergic hypofunction induced in mice by ethylcholine aziridinium ion (AF64A) in vivo. J Pharmacol Exp Ther. červenec 1982;222(1):140-5. Go to PubMed...
    76. Liu J, Ho W-L, Lee NT-K, Carlier PR, Pang Y-P, Han Y-F. Bis(7)-tacrine, a novel acetylcholinesterase inhibitor, reverses AF64A-induced deficits in navigational memory in rats. Neurosci Lett. 24. březen 2000;282(3):165-8. Go to original source...
    77. Pan SY, Yu ZL, Dong H, Lee NTK, Wang H, Fong WF, et al. Evaluation of acute bis(7)-tacrine treatment on behavioral functions in 17-day-old and 30-day-old mice, with attention to drug toxicity. Pharmacol Biochem Behav. 1. duben 2007;86(4):778-83. Go to original source... Go to PubMed...
    78. Yu H, Ho JMK, Kan KKW, Cheng BWH, Li W-M, Zhang L, et al. Development of a high performance liquid chromatography-tandem mass method for determination of bis(7)-tacrine, a promising anti-Alzheimer's dimer, in rat blood. J Pharm Biomed Anal. 3. zaři 2007;44(5):1133-8. Go to original source... Go to PubMed...
    79. Zhang L, Li Z, Yu H, Hua Y, Li WM, Ming LW, et al. Selective and sensitive determination of bis(7)-tacrine, a high erythrocyte binding acetylcholinesterase inhibitor, in rat plasma by high-performance liquid chromatography-tandem mass spectrometry. Biomed Chromatogr BMC. duben 2008;22(4):414-20. Go to original source... Go to PubMed...
    80. Zhang L, Yu H, Li WM, Cheung MC, Pang YP, Gu ZM, et al. Preclinical characterization of intestinal absorption and metabolism of promising anti-Alzheimer's dimer bis(7)-tacrine. Int J Pharm. 5. červen 2008;357(1-2):85-94. Go to original source... Go to PubMed...
    81. Yu H, Li W-M, Kan KKW, Ho JMK, Carlier PR, Pang Y-P, et al. The physicochemical properties and the in vivo AChE inhibition of two potential anti-Alzheimer agents, bis(12)-hupyridone and bis(7)-tacrine. J Pharm Biomed Anal. 7. leden 2008;46(1):75-81. Go to original source... Go to PubMed...
    82. Hancke JL, Burgos RA, Ahumada F. Schisandra chinensis (Turcz.) Baill. Fitoterapia. 1. řijen 1999;70(5):451-71. Go to original source...
    83. Pan SY, Han YF, Carlier PR, Pang YP, Mak DHF, Lam BYH, et al. Schisandrin B protects against tacrine- and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice. Planta Med. březen 2002;68(3):217-20. Go to original source... Go to PubMed...
    84. Li W, Mak M, Jiang H, Wang Q, Pang Y, Chen K, et al. Novel anti-Alzheimer's dimer Bis(7)-cognitin: cellular and molecular mechanisms of neuroprotection through multiple targets. Neurother J Am Soc Exp Neurother. leden 2009;6(1):187-201. Go to original source... Go to PubMed...
    85. Baell JB, Nissink JWM. Seven Year Itch: Pan-Assay Interference Compounds (PAINS) in 2017-Utility and Limitations. ACS Chem Biol. 19. leden 2018;13(1):36-44. Go to original source... Go to PubMed...

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