The effect of HI-6 on cholinesterases and on the cholinergic system of the rat bladder.
OBJECTIVE
The current standard treatment of organophosphate poisoning consists of an administration of anticholinergic drugs and cholinesterase reactivators (oximes). Oximes can react - except their reactivating effect on cholinesterases - directly with cholinoreceptors. HI-6 is an oxime that may have an inhibitory effect on the muscarinic receptors, too.


METHODS
In our work, we have investigated an influence of HI-6 on the acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and on the muscarinic receptors in vitro. The study was conducted using biosensor technique and on the rat bladder using in vitro test (tissue bath; methacholine as muscarinic agonist). IC50 for BChE from human serum was determined to be 1.01x10-6 M and for human erythrocytes AChE 3.31x10-6 M, respectively.


CONCLUSIONS
We assume that the demonstrated contractile response can be attributed to the inhibition of the AChE at the lower concentration and to a predominant inhibition of muscarinic receptor at higher concentration of compound tested.
Soukup
Ondrej
O
Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
Pohanka
Miroslav
M
Tobin
Gunnar
G
Jun
Daniel
D
Fusek
Josef
J
Musilek
Kamil
K
Marek
Jan
J
Kassa
Jiri
J
Kuca
Kamil
K
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D015374:Biosensing Techniques; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D010091:Oximes; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010865:Pilot Projects; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation*
D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D010091:Oximes; D011726:Pyridinium Compounds; D016210:Methacholine Chloride; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C022870:asoxime chloride