Memantine and Its Combination with Acetylcholinesterase Inhibitors in Pharmacological Pretreatment of Soman Poisoning in Mice.

Publisher: Springer Country of Publication: United States NLM ID: 100929017 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-3524 (Electronic) Linking ISSN: 10298428 NLM ISO Abbreviation: Neurotox Res Subsets: MEDLINE

Publication: <2009-> : New York : Springer
Original Publication: [Amsterdam?] : Harwood Academic Publishers,

Acetylcholinesterase/*metabolism ; Cholinesterase Inhibitors/*administration & dosage ; Donepezil/*administration & dosage ; Memantine/*administration & dosage ; Pre-Exposure Prophylaxis/*methods ; Soman/*toxicity; Animals ; Antiparkinson Agents/administration & dosage ; Cholinesterase Inhibitors/toxicity ; Dopamine Agents/administration & dosage ; Drug Therapy, Combination ; Male ; Mice

Nerve agents pose a real threat to both the military and civil populations, but the current treatment of the poisoning is unsatisfactory. Thus, we studied the efficacy of prophylactic use of memantine alone or in combination with clinically used reversible acetylcholinesterase inhibitors (pyridostigmine, donepezil, rivastigmine) against soman. In addition, we tested their influence on post-exposure therapy consisting of atropine and asoxime. Pyridostigmine alone failed to decrease the acute toxicity of soman. But all clinically used acetylcholinesterase inhibitors administered alone reduced the acute toxicity, with donepezil showing the best efficacy. The combination of memantine with reversible acetylcholinesterase inhibitors attenuated soman acute toxicity significantly. The pretreatment administered alone or in combinations influenced the efficacy of post-exposure treatment in a similar fashion: (i) pyridostigmine or memantine alone did not affect the antidotal treatment, (ii) centrally acting reversible acetylcholinesterase inhibitors alone increased the antidotal treatment slightly, (iii) combination of memantine with reversible acetylcholinesterase inhibitors increased the antidotal treatment more markedly. In conclusion, memantine alone failed to decrease the acute toxicity of soman or increase post-exposure antidotal treatment efficacy. The combination of memantine with donepezil significantly increased post-exposure effectiveness (together 5.12, pretreatment alone 1.72). Both drugs, when applied together, mitigate soman toxicity and boost post-exposure treatment.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alozi M, Rawas-Qalaji M (2020) Treating organophosphates poisoning: management challenges and potential solutions. Crit Rev Toxicol 50(9):764–779. https://doi.org/10.1080/10408444.2020.1837069.
Antonijevic B, Stojiljkovic MP (2007) Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. Clin Med Res 5:71–82. (PMID: 10.3121/cmr.2007.701)
Bajgar J (2004) Organophosphate/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis and treatment. Adv Clin Chem 38:151–216. https://doi.org/10.1016/S0065-2423(04)38006-6. (PMID: 10.1016/S0065-2423(04)38006-615521192)
Bajgar J, Fusek J, Kassa J, Kuca K, Jun D (2009) Chemical aspects of pharmacological prophylaxis against nerve agent poisoning. Curr Med Chem 16:2977–2986. https://doi.org/10.2174/092986709788803088.
Bajgar J, Kassa J, Kucera T, Musilek K, Jun D, Kuca K (2019) Some possibilities to study new prophylactics against nerve agents. Mini-Rev Med Chem 19(12):970–979. https://doi.org/10.2174/1389557519666190301112530. (PMID: 10.2174/138955751966619030111253030827238)
Britt JO, Martin JL, Okerberg CV, Dick EJ (2000) Histopathologic changes in the brain, heart and skeletal muscle of rhesus macaque, ten days after exposure to soman (an organophosphorus nerve agent). Comp Med 50(2):133–139. (PMID: 10857003)
Bruins Slot LA, Chopin P, Colpaert FC (2003) Tacrine-Scopolamine Interactions on State-Dependent Retrieval Psychopharmacology (berl) 166:33–39. https://doi.org/10.1007/s00213-002-1292-y. (PMID: 10.1007/s00213-002-1292-y)
Bures J, Kvetina J, Radochova V, Tacheci I, Peterova E, Herman D, Dolezal R, Kopacova M, Rejchrt S, Douda T, Sestak V, Douda L, Karasova JZ (2020) The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs. Plos One 15(1): Article No. e0227781. https://doi.org/10.1371/journal.pone.0227781.
Bures J, Tacheci I, Kvetina J, Radochova V, Prchal L, Kohoutova D, Valis M, Novak M, Dolezal R, Kopacova M, Rejchrt S, Sestak V, Knoblochova V, Peterova E, Zdarova Karasova J (2021) The impact of dextran sodium sulfate-induced gastrointestinal injury on the pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil, and gastric myoelectric activity in experimental pigs. Molecules 26(8):2160. https://doi.org/10.3390/molecules26082160. (PMID: 10.3390/molecules26082160339186388070437)
Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondzic AM, Vasic VM (2013) Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 11:315–335. https://doi.org/10.2174/1570159X11311030006. (PMID: 10.2174/1570159X11311030006241794663648782)
Chambers JE, Dail MB, Meek EC (2020) Oxime-mediated reactivation of organophosphate-inhibited acetylcholinesterase with emphasis on centrally-active oximes. Neuropharmacology 175:No.108201. https://doi.org/10.1016/j.neuropharm.2020.108201.
Chen XY, Magnotta VA, Duff K, Boles Ponto LL, Schultz SK (2006) Donepezil effects on cerebral blood flow in older adults with mild cognitive deficits. J Neuropsychiatr Clin Neurosci 18:178–185. https://doi.org/10.1176/appi.neuropsych.18.2.178. (PMID: 10.1176/appi.neuropsych.18.2.178)
Chen Y (2012) Organophosphate-induced brain damage: mechanisms, neuropsychiatric and neurological consequences, and potential therapeutic strategies. Neurotoxicology 33(3):391–400. https://doi.org/10.1016/j.neuro.2012.03.011. (PMID: 10.1016/j.neuro.2012.03.01122498093)
Cheung J, Rudolph MJ, Burshteyn F, Cassidy MS, Gary EN, Love J, Franklin MC, Height JJ (2012) Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J Med Chem 55:10282–10286. https://doi.org/10.1021/jm300871x. (PMID: 10.1021/jm300871x23035744)
Dunn MA, Hackley BE, Sidell FR (1997) Pretreatment for nerve agent exposure. In: Zajtchuk R, Bellamy RF (eds.) Textbook of military medicine: medical aspects of chemical & biological warfare. Washington DC: Office of the Surgeon General, Department of the Army, pp 181–196.
Gupta RC, Dettbarn WD (1992) Potential of memantine, D-tubocurarine and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents: soman, sarin, tabun and VX. Neurotoxicology 13:649–661. (PMID: 1475066)
Jackson C, Ardinger Ch, Winter KM, McDonough JH, McCarren HS (2019) Validating a model of benzodiazepine refractory nerve agent-induced status epilepticus by evaluating the anticonvulsant and neuroprotective effects of scopolamine, memantine and phenobarbital. J Pharmacol Toxicol Methods 97:1–12. https://doi.org/10.1016/j.vascn.2019.02.006. (PMID: 10.1016/j.vascn.2019.02.006307906236529248)
Karasova JZ, Hroch M, Pohanka M, Hepnarova V, Pejchal J, Kuca K (2020) Pyridostigmine bromide and its relation to Gulf War illness. Toxin Rev 39(2):138–146. https://doi.org/10.1080/15569543.2018.1480496.
Karasova JZ, Hrabinova M, Krejciova M, Jun D, Kuca K (2020) Donepezil and rivastigmine: pharmacokinetic profile and brain-targeting after intramuscular administration in rats. Iran. J Pharm Res 19(3):95–102. https://doi.org/10.22037/ijpr.2019.1100723.
Kassa J (2019) Oxime Research. In: Lukey BJ, Romano JA Jr, Salem H (eds.) Chemical warfare agents − biomedical and psychological effects, medical countermeasures and emergency response. Boca Raton, USA, CRC Press pp 681–695.
Kassa J, Korabecny J, Nepovimova E (2017) The evaluation of benefit of newly prepared reversible inhibitors of acetylcholinesterase and commonly used pyridostigmine as pharmacological pretreatment of soman-poisoned mice. ACTA MEDICA (HK) 60(1):37–43. https://doi.org/10.14712/18059694.2017.45.
Kassa J, Musilek K, Koomlova M, Bajgar J (2012) A comparison of the efficacy of newly developed reversible inhibitors of acetylcholinesterase with commonly used pyridostigmine as pharmacological pretreatment of soman-poisoned mice. Bas Clin Pharmacol Toxicol 110:322–326. https://doi.org/10.1111/j.1742-7843.2011.00808.x. (PMID: 10.1111/j.1742-7843.2011.00808.x)
Korabecny J, Spilovska K, Mezeiova E, Benek O, Juza R, Kaping D, Soukup O (2019) A systematic review on donepezil-based derivatives as potential cholinesterase inhibitors for Alzheimer’s disease. Curr Med Chem 26:5625–5648. https://doi.org/10.2174/0929867325666180517094023. (PMID: 10.2174/092986732566618051709402329768996)
Kosasa T, Kuriya Y, Matsui K, Yamanishi Y (1999) Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats. Eur J Pharmacol 380:101–107. https://doi.org/10.1016/S0014-2999(99)00545-2. (PMID: 10.1016/S0014-2999(99)00545-210513568)
Layish I, Krivoy A, Rotman E, Finkelstein A, Tashma Z, Yehezkelli Y (2005) Pharmacologic prophylaxis against nerve agent poisoning. Isr Med Assoc J 7:182–187. (PMID: 15792266)
Leadbeater L, Inns RH, Ralands JM (1985) Treatment of poisoning by soman. Fund Appl Toxicol 5:S225–S231. https://doi.org/10.1016/0272-0590(85)90132-0. (PMID: 10.1016/0272-0590(85)90132-0)
Lorke DE, Hasan MY, Nurulain SM, Shafiullah M, Kuca K, Petroianu GA (2011) Pretreatment for acute exposure to diisopropylfluorophosphate: in vivo efficacy of various acetylcholinesterase inhibitors. J Appl Toxicol 31:515–523. https://doi.org/10.1002/jat.1589. (PMID: 10.1002/jat.158920981864)
Lorke DE, Kalasz H, Petroianu GA, Tekes K (2008) Entry of oximes into the brain: a review. Curr Med Chem 15:743–753. https://doi.org/10.2174/092986708783955563. (PMID: 10.2174/09298670878395556318393843)
Lorke DE, Petroianu GA (2019) Reversible cholinesterase inhibitors as pretreatment for exposure to organophosphates. A review. J Appl Toxicol 39(1):101–116. https://doi.org/10.1002/jat.3662.
Lupp A, Lücking CH, Koch R, Jackisch R, Feuerstein TJ (1992) Inhibitory effects of the antiparkinsonian drugs memantine and adamantine on N-methyl-D-aspartate-evoked acetylcholine release in the rabbit caudate nucleus in vitro. J Pharmacol Exp Ther 263(2):717–724. (PMID: 1359111)
Marotta G, Basagni F, Rosini M, Minarini A (2020) Memantine derivatives as multitarget agents in Alzheimer’s disease. Molecules 25: No. 4005. https://doi.org/10.3390/molecules 25174005.
Marrs TC, Rice P, Vale JA (2006) The role of oximes in the treatment of nerve agent poisoning in civilian casualties. Toxicol Rev 25:297–323. https://doi.org/10.2165/00139709-200625040-00009. (PMID: 10.2165/00139709-200625040-0000917288500)
McDonough JH, Shih TM (1997) Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology. Neurosci Biobehav Rev 21(5):559–579. https://doi.org/10.1016/S0149-7634(96)00050-4.
McLean MJ, Gupta RC, Dettbarn WD, Wamil AW (1992) Prophylactic and therapeutic efficacy of memantine against seizures produced by soman in the rat. Toxicol Appl Pharmacol 112:95–103. https://doi.org/10.1016/0041-008X(92)90284-Y. (PMID: 10.1016/0041-008X(92)90284-Y1733053)
Mercey G, Verdelet T, Renou J, Kliachyna M, Baati R, Nachon F, Jean L, Renard PY (2012) Reactivators of acetylcholinesterase inhibited by organophosphorus nerve agents. Acc Chem Res 45:756–766. https://doi.org/10.1021/ar2002864. (PMID: 10.1021/ar200286422360473)
Miller SA, Blick DW, Kerenyi SZ, Murphy MR (1993) Efficacy of physostigmine as a pretreatment for organophosphate poisoning. Pharmacol Biochem Behav 44:343–347.  https://doi.org/10.1016/0091-3057(93)90472-6.
Misik J, Kassa J (2014) A comparison of cholinesterase inhibitors in the treatment of quinuclidinyl benzilate-induced behavioural deficit in rats performing the multiple T-maze. J Appl Biomed 12(4):211–217. https://doi.org/10.1016/j.jab.2014.01.006. (PMID: 10.1016/j.jab.2014.01.006)
Myhrer T, Aas P (2016) Pretreatment and prophylaxis against nerve agent poisoning: are undesirable behavioral side effects unavoidable? Neurosci Biobehav Rev 71:657–670. https://doi.org/10.1016/jneubiorev.2016.10.017. (PMID: 10.1016/jneubiorev.2016.10.01727773692)
Nguyen K, Hoffman H, Chakkamparambil B, Grossberg GT (2021) Evaluation of rivastigmine in Alzheimer’s disease. Neurodegen Dis Manag 11(1):35–48. https://doi.org/10.2217/nmt-2020-0052.
Nordberg A (2006) Mechanisms behind the neuroprotective actions of cholinesterase inhibitors in Alzheimer disease. Alzheimer Dis Assoc Disord 20(2):S12–S18. https://doi.org/10.1097/01.wad.0000213804.59187.2d.
Parsons CG, Danysa W, Dekundy A, Pulte I (2013) Memantine and cholinesterase inhibitors: complementary mechanisms in the treatment of Alzheimer’s disease. Neurotox Res 24:358–369. https://doi.org/10.1007/s12640-013-9398-z. (PMID: 10.1007/s12640-013-9398-z236579273753463)
Patocka J, Jun D, Bajgar J, Kuca K (2006) Prophylaxis against nerve agent intoxication. Def Sci J 56:775–784. https://doi.org/10.14429/dsj.56.1941.
Philippens IHCHM, Wolthuis OL, Busker RW, Langenberg JP, Melchers BPC (1996) Side effects of physostigmine as a pretreatment in guinea pigs. Pharmacol Biochem Behav 55:99–105. https://doi.org/10.1016/0091-3057(96)83115-7. (PMID: 10.1016/0091-3057(96)83115-78870044)
Rong X, Jiang LW, Qu MJ, ul Hassan SS, Liu ZC, (2021) Enhancing therapeutic efficacy of donepezil by combined therapy: a comprehensive review. Curr Pharm Des 27(3):332–344. https://doi.org/10.2174/1381612826666201023144836. (PMID: 10.2174/138161282666620102314483633100197)
Shih TM, McDonough JH (1997) Neurochemical mechanisms in soman-induced seizures. J Appl Toxicol 17(4):255–264. https://doi.org/10.1002/(SICI)1099-1263(199707)17:4%3c255:AID-JAT441%3e3.0.CO;2-D. (PMID: 10.1002/(SICI)1099-1263(199707)17:4<255:AID-JAT441>3.0.CO;2-D9285539)
Shih TM, McDonough JH, Koplovitz I (1999) Anticonvulsants for soman-induced seizure activity. J Biomed Sci 6:86–96. https://doi.org/10.1007/BF02256439. (PMID: 10.1007/BF0225643910087439)
Stojiljkovic MP, Skrbic R, Jokanovic M, Kilibarda V, Vukovic M (2019) Prophylactic potential of memantine against soman poisoning in rats. Toxicology 416:62–74. https://doi.org/10.1016/j.tox.2019.01.012.
Takada-Takatori Y, Kume T, Sugimoto M, Katsuki H, Sugimoto H, Akaik A (2006) Acetylcholinesterase inhibitors used in treatment of Alzheimer’s disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3-kinase cascade. Neuropharmacology 51:474–486. https://doi.org/10.1016/j.neuropharm.2006.04.007.
Tallarida R, Murray R (1987) Manual of pharmacological calculation with computer programs. Springer-Verlag, New York.
Tariot PN, Federoff HJ (2003) Current treatment for Alzheimer Disease and future prospects. Alzheimer Dis Assoc Dis 17(Suppl 4):S105–S113. https://doi.org/10.1097/00002093-200307004-00005. (PMID: 10.1097/00002093-200307004-00005)
Tsai MC, Chen ML, Lo SC, Tsai GC (1989) Effects of memantine on the twitch tension of mouse diaphragm. Eur J Pharmacol 160:133–140. https://doi.org/10.1016/0014-2999(89)90662-6. (PMID: 10.1016/0014-2999(89)90662-62714358)
Tsukada H, Sato K, Kakiuchi T, Nishiyama S (2000) Age-related impairment of coupling mechanism between neuronal activation and functional cerebral blood flow response was restored by cholinesterase inhibition: PET study with microdialysis in the awake monkey brain. Brain Res 857:158–164. https://doi.org/10.1016/S0006-8993(99)02394-X. (PMID: 10.1016/S0006-8993(99)02394-X10700563)
Valis M, Masopust J, Vysata O, Hort J, Dolezal R, Tomek J, Misik J, Kuca K, Karasova JZ (2017) Concentration of donepezil in the cerebrospinal fluid of AD patients: evaluation of dosage sufficiency in standard treatment strategy. Neurotox Res 31(1):162–168. https://doi.org/10.1007/s12640-016-9672-y. (PMID: 10.1007/s12640-016-9672-y27718143)
Valis M, Herman D, Vanova N, Masopust J, Vysata O, Hort J, Pavelek Z, Klimova B, Kuca K, Misik J, Karasova JZ (2019) The concentration of memantine in the cerebrospinal fluid of Alzheimer’s disease patients and its consequence to oxidative stress biomarkers. Front Pharmacol 10:943. https://doi.org/10.3389/fphar.2019.00943. (PMID: 10.3389/fphar.2019.00943315551326722429)
Zeb MW, Rias A, Szigeti K (2017) Donepezil: a review of pharmacological characteristics and role in the management of Alzheimer disease. Clin Med Insights Ger 10: No 1179553017695258. https://doi.org/10.1177/1179553017695258.
Zemek F, Drtinova L, Nepovimova E, Sepsova V, Korabecny J, Klimes J, Kuca K (2014) Outcomes of Alzheimer’s disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin Drug Saf 13:759–774. https://doi.org/10.1517/14740338.2014.914168. (PMID: 10.1517/14740338.2014.91416824845946)
Zhou ZJ, Dai XF, Gu X, Sun YG, Zheng G, Zheng J (2005) Memantine alleviates toxicity induced by dichlorvos in rats. J Occup Health 47(2), 96–101. https://doi.org/10.1539/joh.47.96.

Long-term organization development plan - Medical Aspects of Weapons of Mass Destruction Ministerstvo Obrany České Republiky

Keywords: Donepezil; Memantine; Mice; Pyridostigmine; Rivastigmine; Soman

0 (Antiparkinson Agents)
0 (Cholinesterase Inhibitors)
0 (Dopamine Agents)
8SSC91326P (Donepezil)
96-64-0 (Soman)
EC 3.1.1.7 (Acetylcholinesterase)
W8O17SJF3T (Memantine)

Date Created: 20210722 Date Completed: 20220202 Latest Revision: 20220202

20240829

10.1007/s12640-021-00394-2

34292503