Relationship between Oxime-Induced Reactivation of Carbamylated Acetylcholinesterase and Antidotal Efficacy against Carbamate Intoxication

摘要

The Relationship between Oxime-Induced Reactivation of carbamylated Acetylcholinesterase and Antidotal Efficacy against Carbamate Intoxication. Harris, L.W., Talbot, B.G., Lennox, W.J., and Anderson, D.R. (1989) Toxicol. Appl. Pharmacol. 98, 128-133. The efficacy of the oximes pyridimium-2-aldoxime methochloride (2-PAM) and 1-((((4-aminocarbonyl)pyridinio)methoxy)methyl)-2-((hydroxyimino) methyl)pyridinium dichloride (HI-6), in combination with atropine (A+), against lethality by either carbaryl (CA) or physostigmine (Phy) was investigated in rats. The protection by A+, 8 mg/kg, iv, against CA intoxication was reduced by 2-PAM (22 mg/kg, intravenous) 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 A+ alone, At+ 2-PAM, or At+ 2-PAM, or At+ HI-6 at 1 min following Phy provided good protection and resulted in PRs of 7.2, 8.8, nd 23.3, respectively. 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 CA and Phy are both N-methyl carbamates, the data indicate that there is no adverse interaction between 2-PAM or HI-6 and Phy. Keywords: 2-PAM, HI-6, Physostigmine, Carbamate; Oxime, Efficacy antidotes, Reprints. (KT)