The relationship between oxime-induced reactivation of carbamylated acetylcholinesterase and antidotal efficacy against carbamate intoxication

Toxicology and Applied Pharmacology
L W HarrisD R Anderson

Abstract

The efficacy of the oximes pyridinium-2-aldoxime methochloride (2-PAM) and 1-[[[(4-aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydro xyimino) methyl]pyridinium dichloride (HI-6), in combination with atropine (At), against lethality by either carbaryl (CA) or physostigmine (Phy) was investigated in rats. The protection by At, 8 mg/kg, iv, against CA intoxication was reduced by 2-PAM (22 mg/kg, iv) and HI-6 (50 mg/kg, iv) from a protective ratio (PR) of 6.6 to 3.5 and 2.3, respectively. However, in Phy-intoxicated rats, the administration, iv, of At alone, At + 2-PAM, or At + HI-6 at 1 min following Phy provided good protection and resulted in PRs of 7.2, 8.8, and 23.3, respectively. In experiments on decarbamylation of inhibited acetylcholinesterase (AChE), HI-6 and 2-PAM accelerated (p less than 0.05) the decarbamylation of Phy-inhibited AChE in vitro, and HI-6 decreased (p less than 0.05) the inhibition of whole blood AChE in Phy-intoxicated rats. These findings show that the protection was increased substantially by the use of either 2-PAM or HI-6 against Phy-induced lethality, whereas the use of oximes against carbaryl poisoning was contraindicated. Furthermore, even though CA and Phy are both N-methyl carbamates, the data i...Continue Reading

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Citations

Sep 15, 1995·Clinica Chimica Acta; International Journal of Clinical Chemistry·M Rotenberg, S Almog
Sep 1, 1992·Toxicology Letters·C N LieskeW E Sultan
Nov 26, 2009·The American Journal of Emergency Medicine·Yossi RosmanAmir Krivoy
Jun 3, 2011·Journal of Veterinary Emergency and Critical Care·John D Anastasio, Claire R Sharp
Mar 21, 2007·Human & Experimental Toxicology·Maria Mercurio-ZappalaRobert S Hoffman
Jan 24, 2002·Therapeutic Drug Monitoring·Tai C Kwong

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