Matthew K Brittain1, Kevin G McGarry2, Robert A Moyer2, Michael C Babin2, David A Jett3, Gennady E Platoff4, David T Yeung3. 1. Battelle, Columbus, OH, USA brittainm@battelle.org. 2. Battelle, Columbus, OH, USA. 3. National Institute of Neurological Disorders and Stroke (NIH/NINDS), National Institutes of Health, Bethesda, MD, USA. 4. National Institute of Allergy and Infectious Diseases (NIH/NIAID), National Institutes of Health, Bethesda, MD, USA.
Abstract
PURPOSE: Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamate poisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphate poisoning (muscarinic antagonist atropine and the oxime acetylcholinesterase reactivator pralidoxime chloride [2-PAM Cl]) could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates. METHODS: A protective ratio study was conducted in guinea pigs to evaluate the efficacy of atropine and 2-PAM Cl. The ChE activity was determined in both the blood and the cerebral cortex. RESULTS: Coadministration of atropine free base (0.4 mg/kg) and 2-PAM Cl (25.7 mg/kg) demonstrated protective ratios of 2 and 3 against aldicarb and methomyl, respectively, relative to saline. The data reported here show that this protection was primarily mediated by the action of atropine. The reactivator 2-PAM Cl had neither positive nor negative effects on survival. Both blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were significantly reduced at 15 minutes postchallenge but gradually returned to normal within 24 hours. Analysis of cerebral cortex showed that BChE, but not AChE, activity was reduced in animals that succumbed prior to 24 hours after challenge. CONCLUSION: The results suggest that coadministration of atropine and 2-PAM Cl at the currently recommended human equivalent doses for use in the prehospital setting to treat organophosphorus nerve agent and pesticide poisoning would likely also be effective against aldicarb or methomyl poisoning.
PURPOSE:Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamatepoisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphatepoisoning (muscarinic antagonist atropine and the oximeacetylcholinesterase reactivator pralidoxime chloride [2-PAM Cl]) could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates. METHODS: A protective ratio study was conducted in guinea pigs to evaluate the efficacy of atropine and 2-PAM Cl. The ChE activity was determined in both the blood and the cerebral cortex. RESULTS: Coadministration of atropine free base (0.4 mg/kg) and 2-PAM Cl (25.7 mg/kg) demonstrated protective ratios of 2 and 3 against aldicarb and methomyl, respectively, relative to saline. The data reported here show that this protection was primarily mediated by the action of atropine. The reactivator 2-PAM Cl had neither positive nor negative effects on survival. Both blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were significantly reduced at 15 minutes postchallenge but gradually returned to normal within 24 hours. Analysis of cerebral cortex showed that BChE, but not AChE, activity was reduced in animals that succumbed prior to 24 hours after challenge. CONCLUSION: The results suggest that coadministration of atropine and 2-PAM Cl at the currently recommended human equivalent doses for use in the prehospital setting to treat organophosphorus nerve agent and pesticide poisoning would likely also be effective against aldicarb or methomylpoisoning.
Authors: Nadja M Herkert; Saskia Eckert; Peter Eyer; Rudolf Bumm; Georg Weber; Horst Thiermann; Franz Worek Journal: Toxicology Date: 2008-01-20 Impact factor: 4.221
Authors: Kevin G McGarry; Ryan A Bartlett; Nicholas J Machesky; Thomas H Snider; Robert A Moyer; David T Yeung; Matthew K Brittain Journal: Adv Biosci Biotechnol Date: 2013-12-01
Authors: Christina M Wilhelm; Thomas H Snider; Michael C Babin; Gennady E Platoff; David A Jett; David T Yeung Journal: Neurotoxicology Date: 2018-07-26 Impact factor: 4.294