Oxime reactivators and their in vivo and in vitro effects on nicotinic receptors

Title:

Oxime reactivators and their in vivo and in vitro effects on nicotinic receptors

Creator:

Soukup, O., Jan Krůšek, Kaniaková, M., Kumar, U. K., Oz, M., Daniel Jun, Josef Fusek, Kamil Kuča, and Tobin, G.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:e87d2487-f240-4822-8539-eabfbe518f40
uuid:e87d2487-f240-4822-8539-eabfbe518f40

Subject:

Fyziologie člověka a srovnávací fyziologie, organofosfáty, organophosphates, patch-clamp, nicotinic receptors, reactivator, isometric muscle contraction, TE671 cells, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print

Description:

Current treatment of organophosphorus poisoning, resulting in overstimulation and desensitization of muscarinic and nicotinic receptors by acetylcholine (ACh), consists of the administration of atropine and oxime reactiva tors. However, no versatile oxime reactivator has been developed yet and some mortality still remains after application of standard atropine treatment, probably due to its lack of antinicotinic action. In our study, we focused on the interesting non-acetylcholinesterase property of oximes, i.e. antinicotinic effect of reactivators. Two standard reactivators (HI-6, obidoxime) and two new compounds (K027 and K203) were chosen for in vitro (patch clamp) and in vivo (nerve-evoked muscle contraction) testings. Both examinations showed antinicotinic effects of the reactivators. In vitro inhibition of acetylcholine-evoked currents by obidoxime, HI-6 and K203 was equivalent while K027 was less potent. Similar order of potency was observed by the in vivo examinations. We thus confirm previous in vitro results, which describe antinicotinic effects of oxime reactivators, and furthermore, we show in vivo antagonism of oxime reactivators exerted by the inhibition of ACh effect on the nicotinic receptor in the neuromuscular junction. Taking to gether, the effects of tested oxime reactivators indicate an antagonism on both embryonic and adult form of the muscle nicotinic receptors., O. Soukup ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2011 Volume:60 | Number:4

Harvested from:

CDK

Metadata only:

false