Small quaternary inhibitors K298 and K524: cholinesterases inhibition, absorption, brain distribution, and toxicity

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F16%3A43875551" target="_blank" >RIV/60162694:G44__/16:43875551 - isvavai.cz</a>

Alternative codes found

RIV/62690094:18470/16:50004521 RIV/00216208:11150/16:10314133 RIV/00179906:_____/16:10314133

Result on the web

<a href="http://dx.doi.org/10.1007/s12640-015-9582-4" target="_blank" >http://dx.doi.org/10.1007/s12640-015-9582-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12640-015-9582-4" target="_blank" >10.1007/s12640-015-9582-4</a>

Result language

angličtina

Original language name

Small quaternary inhibitors K298 and K524: cholinesterases inhibition, absorption, brain distribution, and toxicity

Original language description

Inhibitors of acetylcholinesterase (AChE) may be used in the treatment of various cholinergic deficits, among them being myasthenia gravis (MG). This paper describes the first in vivo data for promising small quaternary inhibitors (K298 and K524): acute toxicity study, cholinesterase inhibition, absorption, and blood-brain barrier penetration. The newly prepared AChE inhibitors (bis-quinolinium and quinolinium compounds) possess a positive charge in the molecule which ensures that anti-AChE action is restricted to peripheral effect. HPLC-MS was used for determination of real plasma and brain concentration in the pharmacokinetic part of the study, and standard non-compartmental analysis was performed. The maximum plasma concentrations were attained at 30 min (K298; 928.76 +/- A 115.20 ng/ml) and 39 min (K524; 812.40 +/- A 54.96 ng/ml) after i.m. application. Both compounds are in fact able to target the central nervous system. It seems that the difference in the CNS distribution profile depends on an active efflux system. The K524 brain concentration was actively decreased to below an effective level; in contrast, K298 progressively accumulated in brain tissue. Peripheral AChE inhibitors are still first-line treatment in the mild forms of MG. Commonly prescribed carbamates have many severe side effects related to AChE carbamylation. The search for new treatment strategies is still important. Unlike carbamates, these new compounds target AChE via apparent pi-pi or pi-cationic interaction aside at the AChE catalytic site.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FH - Neurology, neuro-surgery, nuero-sciences

OECD FORD branch

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Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

Neurotoxicity Research

ISSN

1029-8428

e-ISSN

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Volume of the periodical

29

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

8

Pages from-to

267-274

UT code for WoS article

000368194200008

EID of the result in the Scopus database

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