Studies on the therapeutic effect of 2-pyridine aldoxime methiodide (2-PAM) in mammals following organophosphorus compound-poisoning (report III): distribution and antidotal effect of 2-PAM in rats.
The metabolic fate of 2-PAM and its antidotal effect on organophosphorus compound poisoning in rats were studied. When 14C-2-PAM was administered intravenously, the amount of 14C reaching the brain was small. Following administration by intramedullary injection, 14C was present in high concentrations in the brain, and 72-90% of the 14C present in the brain corresponded to the unchanged form of 2-PAM. 2-PAM was rapidly excreted into the urine and feces following either intramedullary or intravenous administration. The half-life of 2-PAM in the brain following intramedullary administration was 1.52 hr. Intramedullary administration of 2-PAM to rats poisoned with fenitrothion or malathion enabled their survival and induced reactivation of brain cholinesterase.
Uehara
S
S
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Hiromori
T
T
Isobe
N
N
Suzuki
T
T
Kato
T
T
Miyamoto
J
J
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002802:Cholinesterases / Q000378:metabolism; D004789:Enzyme Activation; D005278:Fenitrothion / Q000506:poisoning; D006207:Half-Life; D007267:Injections; D007275:Injections, Intravenous; D008294:Malathion / Q000506:poisoning; D008297:Male; D062025:Organophosphate Poisoning; D011041:Poisoning / Q000188:drug therapy; D011220:Pralidoxime Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013346:Subarachnoid Space; D014018:Tissue Distribution
D000931:Antidotes; D002801:Cholinesterase Reactivators; D011220:Pralidoxime Compounds; D002802:Cholinesterases; C028797:pralidoxime; D008294:Malathion; D005278:Fenitrothion