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- Soukup, O, et al.
(author)
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Novel acetylcholinesterase reactivator K112 and its cholinergic properties.
- 2010
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In: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. - : Elsevier BV. - 1950-6007. ; 64:8, s. 541-5
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Journal article (peer-reviewed)abstract
- The oxime reactivator K112 is a member of the new group of xylene linker-containing AChE reactivators. Its cholinergic properties could be of importance at OP poisoning and are not related to the AChE reactivation that has been studied. It has been found that, despite of reactivating potency, this compound has additional effects. These cholinergic effects include a weak inhibition of AChE (IC(50)=43.8+/-4.88muM), inhibition of binding to the porcine muscarinic M2 receptor (IC(50)=4.36muM) and finally, the inhibition of HACU (68.4+/-9.9%), a key regulatory step in the synthesis of ACh. The inhibition of the binding of (3H)-HC-3 (64.7+/-4.7%) and the influence on the membrane fluidity have also been observed. Blocking properties of K112 on the muscarinic receptors have been revealed in the in vitro experiment (rat urinary bladder) and in the in vivo experiment (rat heart BPM) as well. All these cholinergic properties could significantly contribute to the antidotal effect of K112 at the poisoning by the organophosphates.
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- Soukup, O, et al.
(author)
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Oxime reactivators and their in vivo and in vitro effects on nicotinic receptors.
- 2011
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In: Physiological research / Academia Scientiarum Bohemoslovaca. - 1802-9973. ; 60:4, s. 679-686
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Journal article (peer-reviewed)abstract
- 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 reactivators. 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 and in vitro (patch clamp) and in vivo (nerve-evoked muscle contraction) testings were applied. 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 examiations. 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 inhibition of the ACh effect on the nicotinic receptor in the neuromuscular junction. Taking together, the effects of tested oxime reactivators indicate an antagonism on both embryonic and adult form of the nicotinic receptors.
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