Tacrine and its 7-methoxy derivate; time-change concentration in plasma and brain tissue and basic toxicological profile in rats

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F19%3A50015742" target="_blank" >RIV/62690094:18470/19:50015742 - isvavai.cz</a>

Result on the web

<a href="https://www.tandfonline.com/doi/abs/10.1080/01480545.2019.1566350?journalCode=idct20" target="_blank" >https://www.tandfonline.com/doi/abs/10.1080/01480545.2019.1566350?journalCode=idct20</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/01480545.2019.1566350" target="_blank" >10.1080/01480545.2019.1566350</a>

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 &apos; 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 18(th) 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 (AUC(brain)/AUC(plasma)) 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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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30108 - Toxicology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

DRUG AND CHEMICAL TOXICOLOGY

ISSN

0148-0545

e-ISSN

—

Volume of the periodical

Neuveden

Issue of the periodical within the volume

JUN

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

1-8

UT code for WoS article

000473962700001

EID of the result in the Scopus database

2-s2.0-85068527306