Disposition and metabolism of acetylcholinesterase reactivators 2PAM-I, TMB4 and R665 in rats submitted to organophosphate poisoning

• Published in: Xenobiotica Vol. 21; no. 5; pp. 583 - 595
• Main Authors: Garrigue, H, Maurizis, J.C, Madelmont, J.C, Nicolas, C, Meyniel, J.M, Louvel, A, Demerseman, P, Sentenac-Roumanou, H, Veyre, A
• Format: Journal Article
• Language: English
• Published: England 1991
• Subjects: Acetylcholinesterase; Animals; blood plasma; Carbon Radioisotopes; Cholinesterase Reactivators - pharmacokinetics; enzyme activators; feces; isotope labeling; kidneys; liver; Male; metabolism; Organophosphate Poisoning; organophosphorus compounds; Oximes - pharmacokinetics; Poisoning - metabolism; Pralidoxime Compounds - pharmacokinetics; Rats; Rats, Inbred Strains; Tissue Distribution; Trimedoxime - pharmacokinetics; urine
• ISSN: 0049-8254; 1366-5928
• DOI: 10.3109/00498259109039498

The dispositions of the acetylcholinesterase reactivators: 2PAM-1, TMB4 and R665, labelled with 14C on the oxime group, have been studied in normal rats and rats poisoned by the organophosphates Soman and A4. For all three compounds, radioactivity was eliminated mostly in the urine (60-90% dose in 24 h). Faecal elimination was low (5.8-17.2% in 72 h). All three compounds concentrated in kidney, but only 2PAM-I and R665 concentrated in liver. TMB4 and R665 concentrated in mucopolysaccharide-containing tissues such as cartilage and intervertebral disc. Other tissues were weakly and uniformly labelled. Soman poisoning does not modify the kinetic parameters of both compounds, but A4 poisoning increases 2PAM-I tissue concentration. Chromatography of urine and plasma showed only unchanged 2PAM-I, TMB4 and R665 in both healthy and poisoned animals. Despite the high concentration of 2PAM-I and R665 in liver, these oximes are not metabolized.