Tacrine and its 7-methoxy derivate; time-change concentration in plasma and brain tissue and basic toxicological profile in rats
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F21%3A10409701" target="_blank" >RIV/00216208:11150/21:10409701 - isvavai.cz</a>
Alternative codes found
RIV/62690094:18470/19:50015742 RIV/00179906:_____/21:10409701 RIV/62690094:18470/21:50015742 RIV/60162694:G44__/21:00555488
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=CmIMqeS4Ru" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=CmIMqeS4Ru</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/01480545.2019.1566350" target="_blank" >10.1080/01480545.2019.1566350</a>
Alternative languages
Result language
angličtina
Original language name
Tacrine and its 7-methoxy derivate; time-change concentration in plasma and brain tissue and basic toxicological profile in rats
Original language description
The search for tacrine derivatives, as potential Alzheimer's disease treatment, is still being at the forefront of scientific efforts. 7-MEOTA was found to be a potent, centrally active acetylcholinesterase inhibitor free of the serious side effects observed for tacrine. Unfortunately, a relevant argumentation about pharmacokinetics and potential toxicity is incomplete; information about tacrine derivatives absorption and especially CNS penetration are still rare as well as detailed toxicological profile in vivo. Although the structural changes between these compounds are not so distinctive, differences in plasma profile and CNS targeting were found. The maximum plasma concentration were attained at 18th min (tacrine; 38.20 +- 3.91 ng/ml and 7-MEOTA; 88.22 +- 15.19 ng/ml) after i.m. application in rats. Although the brain profiles seem to be similar; tacrine achieved 19.34 +- 0.71 ng/ml in 27 min and 7-MEOTA 15.80 +- 1.13 ng/ml in 22 min; the tacrine Kp (AUCbrain/AUCplasma) fit 1.20 and was significantly higher than 7-MEOTA Kp 0.10. Administration of tacrine and 7-MEOTA showed only mild elevation of some biochemical markers following single p.o. application in 24 hours and 7 days. Also histopathology revealed only mild-to-moderate changes following repeated p.o. administration for 14 days. It seems that small change in tacrine molecule leads to lower ability to penetrate through the biological barriers. The explanation that lower p.o. acute toxicity of 7-MEOTA depends only on differences in metabolic pathways may be now revised to newly described differences in pharmacokinetic and toxicological profiles.
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/GA18-13283S" target="_blank" >GA18-13283S: The influence of experimental gastrointestinal injury and inflammation on pharmacokinetics of Alzheimer's disease drugs</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Drug and Chemical Toxicology
ISSN
0148-0545
e-ISSN
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Volume of the periodical
44
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
207-214
UT code for WoS article
000473962700001
EID of the result in the Scopus database
2-s2.0-85068527306