On the use of diazepam and pro-diazepam (2-benzoyl-4-chloro-N-methyl-N-lysylglycin anilide), as adjunct antidotes in the treatment of organophosphorus intoxication in the guinea-pig.
Diazepam and pro-diazepam (2-benzoyl-4-chloro-N-methyl-N-lysylglycin anilide) have been used as adjunct antidotes to pyridostigmine and atropine against the organophosphate, soman, in the guinea-pig. Both added significant protection to the pyridostigmine/atropine treatment. Animals pretreated with diazepam, 60 min before soman, were "better" protected than animals given an equimolar dose of pro-diazepam therapeutically 1 min after soman. A pretreatment with diazepam for three days further increased the protection. A therapeutic dose of pro-diazepam, 1 min after soman, gave no further protection, to the three day diazepam pretreatment. The serum concentrations of diazepam (given i.p.) and desmethyldiazepam (given i.m.) were determined by GLC after diazepam (i.p.) and pro-diazepam (i.m.) were given. The protection, relative to the control, provided by the diazepam pretreatment (60 min before and for three days before soman) correlated linearly, r = 0.9898, with the serum values of diazepam achieved at these times. Our data suggest that diazepam as adjunct to pyridostigmine and atropine administered as pretreatment gives a "safer" protection, than an equimolar dose of pro-diazepam given therapeutically.
Karlsson
B
B
Swedish Defence Research Establishment Department of NBC Defence, Umeå.
Lindgren
B
B
Millquist
E
E
Sandberg
M
M
Sellström
A
A
D000818:Animals; D000931:Antidotes; D002849:Chromatography, Gas; D003975:Diazepam / Q000627:therapeutic use*; D004151:Dipeptides / Q000627:therapeutic use*; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008297:Male; D062025:Organophosphate Poisoning; D012999:Soman / Q000506:poisoning
D000931:Antidotes; D004151:Dipeptides; C065249:pro-diazepam; D012999:Soman; D003975:Diazepam