Characterization of the anticholinergic properties of obidoxime; functional examinations of the rat atria and the urinary bladder.
Obidoxime, a well-known bis-pyridinium reactivator, is often the preferred antidote of organophosphorus poisoning caused by pesticides and tabun. It is also considered to be an allosteric modulator of muscarinic receptors, preferably M2 sub-type. This study compared the effect of obidoxime and atropine in vivo and in vitro on the cholinergic stimulation of the rat heart (M2) and the urinary bladder (M3). The results showed that obidoxime exerts anti-muscarinic effects, that may play an important role in the treatment of organophosphourus poisoning, and that the muscarinic receptor inhibition profile shows M2 receptor selectivity. This anti-muscarinic effect is much smaller that the effect of atropine and might be due to the allosteric inhibition of the receptors. The results also indicate that the acetylcholinesterase inhibition and the muscarinic receptor antagonism occur at different concentrations and dose levels.
Soukup
Ondrej
O
Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. soukup.ondrej@seznam.cz
Tobin
Gunnar
G
Kumar
Uday Killi
UK
Jun
Daniel
D
Fusek
Josef
J
Kuca
Kamil
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009768:Obidoxime Chloride / Q000737:chemistry / Q000494:pharmacology*; D062025:Organophosphate Poisoning; D051381:Rats; D001743:Urinary Bladder / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D009768:Obidoxime Chloride; D001285:Atropine