Abstract | AIMS: 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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Authors | Jan Misik, Jan Korabecny, Eugenie Nepovimova, Pavla Cabelova, Jiri Kassa |
Journal | Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
(Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub)
Vol. 159
Issue 4
Pg. 547-53
(Dec 2015)
ISSN: 1804-7521 [Electronic] Czech Republic |
PMID | 25690521
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cholinesterase Inhibitors
- Indans
- Muscarinic Antagonists
- Nootropic Agents
- Piperidines
- Tacrine
- Quinuclidinyl Benzilate
- Donepezil
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Topics |
- Animals
- Behavior, Animal
(drug effects)
- Cholinesterase Inhibitors
(pharmacology)
- Donepezil
- Dose-Response Relationship, Drug
- Indans
(pharmacology)
- Male
- Maze Learning
(drug effects)
- Muscarinic Antagonists
(toxicity)
- Nootropic Agents
(pharmacology)
- Piperidines
(pharmacology)
- Quinuclidinyl Benzilate
(toxicity)
- Rats, Wistar
- Tacrine
(analogs & derivatives, pharmacology)
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