Cholinesterase Inhibitor 6-Chlorotacrine - In Vivo Toxicological Profile and Behavioural Effects
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F18%3A10374738" target="_blank" >RIV/00179906:_____/18:10374738 - isvavai.cz</a>
Alternative codes found
RIV/60162694:G44__/18:43889492
Result on the web
<a href="https://doi.org/10.2174/1567205015666171212105412" target="_blank" >https://doi.org/10.2174/1567205015666171212105412</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1567205015666171212105412" target="_blank" >10.2174/1567205015666171212105412</a>
Alternative languages
Result language
angličtina
Original language name
Cholinesterase Inhibitor 6-Chlorotacrine - In Vivo Toxicological Profile and Behavioural Effects
Original language description
Background: 6-chlorotacrine is a cholinesterase inhibitor showing good inhibitory potential, even better than parent compound tacrine, in vitro. Despite tacrine scaffold is broadly used for design and synthesis of novel compounds with anti-Alzheimer's potential, no in vivo effects have been investigated so far. Thus, basic toxicological and behavioural evaluation has been carried out throughout this study. Methods: Maximum tolerated dose (MTD) and median lethal dose (LD50) were assessed in BALB/c mice and Wistar rats. Behavioural effects were observed in rats performing the multiple T-maze test, the water maze test and the step-through passive avoidance test. All outcomes were compared with the effects of parent compound - tacrine. Results: The toxicity of 6-chlorotacrine was increased compared to tacrine with MTD 6.0/5.0 mg.kg-1 (i.m., male/female mice), 6.0/5.0 mg.kg-1 (i.p., male/female rats) and LD50 9.0 mg.kg-1 (male rats). At MTD doses, no histopathological changes and blood biochemistry abnormalities were observed except decreased plasma creatinine levels. 6-chlorotacrine showed good effects in the reversal of quinuclidinyl benzilate-induced amnesia. Best results were achieved at the dose of 1.8 mg.kg-1 (20% LD50) in the water maze test; the pro-cognitive effect was stronger than that of tacrine (5.2 mg.kg-1, 20% LD50). Other doses tested (0.9 mg.kg-1 and 2.7 mg.kg-1) showed similar effects as tacrine in the water maze, multiple T-maze and passive avoidance test. Conclusion: Observed effects predetermined 6-chlorotacrine as a potent parent compound for the synthesis of novel multifactorial drugs intended to the treatment of Alzheimer's disease. Even though 6- chlorotacrine showed in vivo beneficial effect with no signs of toxicity, further tests on the field of biochemistry and pharmacology are essential to disclose the exact mechanism of action, safety evaluation and the metabolic fate of the compound after the repeated administration
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/GA16-08554S" target="_blank" >GA16-08554S: Novel hybrid compounds in the cognitive decline caused by neurodegeneration</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Current Alzheimer Research
ISSN
1567-2050
e-ISSN
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Volume of the periodical
15
Issue of the periodical within the volume
6
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
9
Pages from-to
552-560
UT code for WoS article
000429368100005
EID of the result in the Scopus database
2-s2.0-85046710851