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

Abstract

1. The dispositions of the acetylcholinesterase reaetivators: 2PAM-I, 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.

2. 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).

3. 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.

4. Chromatography of urine and plasma showed only unchaged 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.