Efficacy of Recommended Prehospital Human Equivalent Doses of Atropine and Pralidoxime Against the Toxic Effects of Carbamate Poisoning in the Hartley Guinea Pig.
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.



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.



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.



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.
Battelle, Columbus, OH, USA brittainm@battelle.org.
Matthew K
MK
Brittain
Battelle, Columbus, OH, USA.
Kevin G
KG
McGarry
Battelle, Columbus, OH, USA.
Robert A
RA
Moyer
Battelle, Columbus, OH, USA.
Michael C
MC
Babin
National Institute of Neurological Disorders and Stroke (NIH/NINDS), National Institutes of Health, Bethesda, MD, USA.
David A
DA
Jett
National Institute of Allergy and Infectious Diseases (NIH/NIAID), National Institutes of Health, Bethesda, MD, USA.
Gennady E
GE
Platoff
National Institute of Neurological Disorders and Stroke (NIH/NINDS), National Institutes of Health, Bethesda, MD, USA.
David T
DT
Yeung
D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000448:Aldicarb / Q000633:toxicity; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage* / Q000627:therapeutic use; D001285:Atropine / Q000008:administration & dosage* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000008:administration & dosage* / Q000627:therapeutic use; D004632:Emergency Medical Services; D006168:Guinea Pigs; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D008297:Male; D008724:Methomyl / Q000633:toxicity; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D062025:Organophosphate Poisoning / Q000188:drug therapy*; D011220:Pralidoxime Compounds / Q000008:administration & dosage* / Q000627:therapeutic use
D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D007306:Insecticides; D018727:Muscarinic Antagonists; D011220:Pralidoxime Compounds; D008724:Methomyl; D001285:Atropine; D000448:Aldicarb; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C028797:pralidoxime
2-PAM Cl; atropine; carbamates; pesticide