Harris_1989_Toxicol.Appl.Pharmacol_98_128

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 indicate that there is no adverse interaction between 2-PAM or HI-6 and Phy