The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test

Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeu...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Jan Misik [verfasserIn] Jan Korabecny [verfasserIn] Eugenie Nepovimova [verfasserIn] Pavla Cabelova [verfasserIn] Jiri Kassa [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	acetylcholine acetylcholinesterase alzheimer disease spatial orientation donepezil tacrine

Übergeordnetes Werk:	In: Biomedical Papers - Palacký University Olomouc, Faculty of Medicine and Dentistry, 2019, 159(2015), 4, Seite 547-553
Übergeordnetes Werk:	volume:159 ; year:2015 ; number:4 ; pages:547-553

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.5507/bp.2015.006

Katalog-ID:	DOAJ035974982

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allfields	10.5507/bp.2015.006 doi (DE-627)DOAJ035974982 (DE-599)DOAJcb79795466eb4737ba4b47a2a2747e2f DE-627 ger DE-627 rakwb eng Jan Misik verfasserin aut The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease. acetylcholine acetylcholinesterase alzheimer disease spatial orientation donepezil tacrine Medicine R Jan Korabecny verfasserin aut Eugenie Nepovimova verfasserin aut Pavla Cabelova verfasserin aut Jiri Kassa verfasserin aut In Biomedical Papers Palacký University Olomouc, Faculty of Medicine and Dentistry, 2019 159(2015), 4, Seite 547-553 (DE-627)50107788X (DE-600)2205906-4 18047521 nnns volume:159 year:2015 number:4 pages:547-553 https://doi.org/10.5507/bp.2015.006 kostenfrei https://doaj.org/article/cb79795466eb4737ba4b47a2a2747e2f kostenfrei https://biomed.papers.upol.cz/artkey/bio-201504-0006_The_effects_of_novel_7-MEOTA-donepezil_like_hybrids_and_N-alkylated_tacrine_analogues_in_the_treatment_of_quinu.php kostenfrei https://doaj.org/toc/1213-8118 Journal toc kostenfrei https://doaj.org/toc/1804-7521 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 159 2015 4 547-553
spelling	10.5507/bp.2015.006 doi (DE-627)DOAJ035974982 (DE-599)DOAJcb79795466eb4737ba4b47a2a2747e2f DE-627 ger DE-627 rakwb eng Jan Misik verfasserin aut The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease. acetylcholine acetylcholinesterase alzheimer disease spatial orientation donepezil tacrine Medicine R Jan Korabecny verfasserin aut Eugenie Nepovimova verfasserin aut Pavla Cabelova verfasserin aut Jiri Kassa verfasserin aut In Biomedical Papers Palacký University Olomouc, Faculty of Medicine and Dentistry, 2019 159(2015), 4, Seite 547-553 (DE-627)50107788X (DE-600)2205906-4 18047521 nnns volume:159 year:2015 number:4 pages:547-553 https://doi.org/10.5507/bp.2015.006 kostenfrei https://doaj.org/article/cb79795466eb4737ba4b47a2a2747e2f kostenfrei https://biomed.papers.upol.cz/artkey/bio-201504-0006_The_effects_of_novel_7-MEOTA-donepezil_like_hybrids_and_N-alkylated_tacrine_analogues_in_the_treatment_of_quinu.php kostenfrei https://doaj.org/toc/1213-8118 Journal toc kostenfrei https://doaj.org/toc/1804-7521 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 159 2015 4 547-553
allfields_unstemmed	10.5507/bp.2015.006 doi (DE-627)DOAJ035974982 (DE-599)DOAJcb79795466eb4737ba4b47a2a2747e2f DE-627 ger DE-627 rakwb eng Jan Misik verfasserin aut The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease. acetylcholine acetylcholinesterase alzheimer disease spatial orientation donepezil tacrine Medicine R Jan Korabecny verfasserin aut Eugenie Nepovimova verfasserin aut Pavla Cabelova verfasserin aut Jiri Kassa verfasserin aut In Biomedical Papers Palacký University Olomouc, Faculty of Medicine and Dentistry, 2019 159(2015), 4, Seite 547-553 (DE-627)50107788X (DE-600)2205906-4 18047521 nnns volume:159 year:2015 number:4 pages:547-553 https://doi.org/10.5507/bp.2015.006 kostenfrei https://doaj.org/article/cb79795466eb4737ba4b47a2a2747e2f kostenfrei https://biomed.papers.upol.cz/artkey/bio-201504-0006_The_effects_of_novel_7-MEOTA-donepezil_like_hybrids_and_N-alkylated_tacrine_analogues_in_the_treatment_of_quinu.php kostenfrei https://doaj.org/toc/1213-8118 Journal toc kostenfrei https://doaj.org/toc/1804-7521 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 159 2015 4 547-553
allfieldsGer	10.5507/bp.2015.006 doi (DE-627)DOAJ035974982 (DE-599)DOAJcb79795466eb4737ba4b47a2a2747e2f DE-627 ger DE-627 rakwb eng Jan Misik verfasserin aut The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease. acetylcholine acetylcholinesterase alzheimer disease spatial orientation donepezil tacrine Medicine R Jan Korabecny verfasserin aut Eugenie Nepovimova verfasserin aut Pavla Cabelova verfasserin aut Jiri Kassa verfasserin aut In Biomedical Papers Palacký University Olomouc, Faculty of Medicine and Dentistry, 2019 159(2015), 4, Seite 547-553 (DE-627)50107788X (DE-600)2205906-4 18047521 nnns volume:159 year:2015 number:4 pages:547-553 https://doi.org/10.5507/bp.2015.006 kostenfrei https://doaj.org/article/cb79795466eb4737ba4b47a2a2747e2f kostenfrei https://biomed.papers.upol.cz/artkey/bio-201504-0006_The_effects_of_novel_7-MEOTA-donepezil_like_hybrids_and_N-alkylated_tacrine_analogues_in_the_treatment_of_quinu.php kostenfrei https://doaj.org/toc/1213-8118 Journal toc kostenfrei https://doaj.org/toc/1804-7521 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 159 2015 4 547-553
allfieldsSound	10.5507/bp.2015.006 doi (DE-627)DOAJ035974982 (DE-599)DOAJcb79795466eb4737ba4b47a2a2747e2f DE-627 ger DE-627 rakwb eng Jan Misik verfasserin aut The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease. acetylcholine acetylcholinesterase alzheimer disease spatial orientation donepezil tacrine Medicine R Jan Korabecny verfasserin aut Eugenie Nepovimova verfasserin aut Pavla Cabelova verfasserin aut Jiri Kassa verfasserin aut In Biomedical Papers Palacký University Olomouc, Faculty of Medicine and Dentistry, 2019 159(2015), 4, Seite 547-553 (DE-627)50107788X (DE-600)2205906-4 18047521 nnns volume:159 year:2015 number:4 pages:547-553 https://doi.org/10.5507/bp.2015.006 kostenfrei https://doaj.org/article/cb79795466eb4737ba4b47a2a2747e2f kostenfrei https://biomed.papers.upol.cz/artkey/bio-201504-0006_The_effects_of_novel_7-MEOTA-donepezil_like_hybrids_and_N-alkylated_tacrine_analogues_in_the_treatment_of_quinu.php kostenfrei https://doaj.org/toc/1213-8118 Journal toc kostenfrei https://doaj.org/toc/1804-7521 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 159 2015 4 547-553
language	English
source	In Biomedical Papers 159(2015), 4, Seite 547-553 volume:159 year:2015 number:4 pages:547-553
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author	Jan Misik
spellingShingle	Jan Misik misc acetylcholine misc acetylcholinesterase misc alzheimer disease misc spatial orientation misc donepezil misc tacrine misc Medicine misc R The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test
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topic_title	The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test acetylcholine acetylcholinesterase alzheimer disease spatial orientation donepezil tacrine
topic	misc acetylcholine misc acetylcholinesterase misc alzheimer disease misc spatial orientation misc donepezil misc tacrine misc Medicine misc R
topic_unstemmed	misc acetylcholine misc acetylcholinesterase misc alzheimer disease misc spatial orientation misc donepezil misc tacrine misc Medicine misc R
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title	The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test
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title_full	The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test
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title_sort	effects of novel 7-meota-donepezil like hybrids and n-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple t-maze test
title_auth	The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test
abstract	Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease.
abstractGer	Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease.
abstract_unstemmed	Aims: The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease.
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title_short	The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test
url	https://doi.org/10.5507/bp.2015.006 https://doaj.org/article/cb79795466eb4737ba4b47a2a2747e2f https://biomed.papers.upol.cz/artkey/bio-201504-0006_The_effects_of_novel_7-MEOTA-donepezil_like_hybrids_and_N-alkylated_tacrine_analogues_in_the_treatment_of_quinu.php https://doaj.org/toc/1213-8118 https://doaj.org/toc/1804-7521
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For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods: Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results: QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">acetylcholine</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">acetylcholinesterase</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">alzheimer disease</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">spatial orientation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">donepezil</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">tacrine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield 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The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test

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