title: The summary on non-reactivation cholinergic properties of oxime reactivators: the interaction with muscarinic and nicotinic receptors.
abstract: Organophosphorus inhibitors (OP) of acetylcholinesterase (AChE) represent a group of highly toxic compounds. The treatment of OP intoxication is, however, insufficiently ensured. Currently, two main categories of drugs-anticholinergics and oxime reactivators- are employed as antidotes. Oximes have been reported to act at several levels of the cholinergic transmission, and among the non-reactivation effects, the interaction with cholinergic receptors stands out. This review addresses issues correlated with non-reactivating effects of oxime reactivators with a special focus on the muscarinic and nicotinic receptors, but involvement of other cholinergic structures such as AChE and choline uptake carriers are discussed too. It can be concluded that the oxime reactivators show a variation in their antagonistic effect on the muscarinic and nicotinic receptors, which is likely to be of significance in the treatment of OP poisoning. In vitro data reported oximes to exert higher efficacy on the muscarinic M2 subtype than on the AChE. However, this effect seemed to be subtype specific since the antagonistic M3 effect was lower. Also, and importantly, the antimuscarinic effect was larger than that on nicotinic receptors. Even though atropine showed a much higher muscarinic antagonism, it is supposed that non-reactivation properties of oxime reactivators play a significant role in the treatment of OP poisoning.
authors.affiliation: Biomedical Research Center, University Hospital of Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Soukup
authors.forename: D
authors.initials: D
authors.lastname: Jun
authors.forename: G
authors.initials: G
authors.lastname: Tobin
authors.forename: K
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use; D001285:Atropine / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009119:Muscle Contraction / Q000187:drug effects; D062025:Organophosphate Poisoning / Q000188:drug therapy / Q000378:metabolism; D010755:Organophosphates / Q000378:metabolism / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
chemical_list: D000931:Antidotes; D018678:Cholinergic Agents; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D001285:Atropine; D000110:Acetylcholinesterase; D002794:Choline