Increasing oxime efficacy by blood-brain barrier modulation

One of the shortcomings of current treatment of nerve agent poisoning is that oximes hardly penetrate the blood-brain barrier (BBB), whereas nerve agents easily do. Increasing the concentration of oximes in the brain, would therefore provide an attractive approach to improve medical countermeasures. An explanation for limited penetration might...

Toxicokinetics of the nerve agent (±)-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration

In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(±)P(±)-soman and (±)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (±)-VX. A validated method was developed to determine blood levels of (±)-VX by means of achiral gas chromatography at blood levels ≥10 pg/ml. The ratio of the...

Intravenous and inhalation toxicokinetics of sarin stereoisomers in atropinized guinea pigs

We report the first toxicokinetic studies of (±)-sarin. The toxicokinetics of the stereoisomers of this nerve agent were studied in anesthetized, atropinized, and restrained guinea pigs after intravenous bolus administration of a dose corresponding to 0.8 LD50 and after nose-only exposure to vapor concentrations yielding 0.4 and 0.8 LCt50 in an...

Low level nose-only exposure to the nerve agent soman: Toxicokinetics of soman stereoisomers and cholinesterase inhibition in atropinized guinea pigs

In order to initiate a quantitative basis for the toxicology of low level exposure to nerve agents, the toxicokinetics of soman stereoisomers during nose-only exposure for 5 h to 20 ppb (160 μg/m3) of C(±)P(±)- soman in air were studied in restrained, anesthetized, and atropinized guinea pigs. The concentrations of the toxic C(±)P(-)-soman...

Efficacy of HI-6 and HLÖ-7 in preventing incapacitation following nerve agent poisoning

The therapeutic efficacy of the oximes HI-6 and HLo-7 (132.5 μmol/kg), in combination with atropine, in soman- or tabun-intoxicated guinea pigs was compared, particularly with respect to recovery of shuttlebox performance and electroencephalograms (EEGs). After 1.5 x LD50 soman SC, therapy with HI-6 or HLo-7 resulted in survival of 87.5% of the...

Behavioral performance, brain histology, and EEG sequela after immediate combined atropine/diazepam treatment of soman-intoxicated rats

It is known that rats poisoned with near-lethal doses of pinacolyl methylphosphonofluoridate (soman) develop brain lesions, particularly when convulsions are induced. When rats were intoxicated with a LD50 of soman and treated immediately thereafter with a combination of low doses of atropine and diazepam (LOW AS/DZ treatment), large decrements...