Current approaches to enhancing oxime reactivator delivery into the brain

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F19%3A00536978" target="_blank" >RIV/60162694:G44__/19:00536978 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/19:10400302

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0300483X19301581" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0300483X19301581</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2019.05.006" target="_blank" >10.1016/j.tox.2019.05.006</a>

Result language

angličtina

Original language name

Current approaches to enhancing oxime reactivator delivery into the brain

Original language description

The misuse of organophosphate compounds still represents a current threat worldwide. Treatment of poisoning with organophosphates (OPs) remains unsatisfactorily resolved despite the extensive investment in research in academia. There are no universal, effective and centrally-active acetylcholinesterase (AChE) reactivators to countermeasure OP intoxication. One major obstacle is to overcome the blood-brain barrier (BBB). The central compartment is readily accessible by the OPs which are lipophilic bullets that can easily cross the BBB, whereas first-line therapeutics, namely oxime-based AChE reactivators and atropine, do not cross or do so rather slowly. The limitation of oxime-based AChE reactivators can be ascribed to their chemical nature, bearing a positive charge which is essential either for their AChE affinity or their reactivating potency. The aim of this article is to review the methods for targeting the brain by oxime reactivators that have been developed so far. Approaches using prodrugs, lipophilicity enhancement, or sugar-based oximes have been rather unsuccessful. However, other strategies have been more promising, such as the use of nanoparticles or co-administration of the reactivator with efflux transporter inhibitors. Encouraging results have also been associated with intranasal delivery, but research in this field is still at the beginning. Further research of auspicious approaches is inevitable

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/NV17-32801A" target="_blank" >NV17-32801A: Centrally acting antidotes for the treatment of organophosphorus poisoning</a><br>

Continuities

S - Specificky vyzkum na vysokych skolach<br>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

Toxicology

ISSN

0300-483X

e-ISSN

0300-483X

Volume of the periodical

423

Issue of the periodical within the volume

1

Country of publishing house

IE - IRELAND

Number of pages

9

Pages from-to

75-83

UT code for WoS article

000483417200006

EID of the result in the Scopus database

2-s2.0-85066068619