Measurement of the oxime HI-6 after peripheral administration in tandem with neurotransmitter levels in striatal dialysates: effects of soman intoxication.
In the present study, the technique of microdialysis combined with tandem high-performance liquid chromatography was used to determine the striatal levels of HI-6 and neurotransmitters following peripheral administration of HI-6 (50 mg/kg i.m.) in conscious, freely moving rats. The results were compared with those obtained in animals given soman (135 micrograms/kg i.p.) 1 min before HI-6 (50 mg/kg i.m.). Principal component analysis was used to study the effects of the different treatments on neurotransmitters and signs of poisoning. In all animals given HI-6, maximum levels of HI-6 appeared in the second 20-min fraction after administration of HI-6, then gradually declined, reaching the lower limits of detection after 3 hr. There was a correlation between severity of poisoning and neurochemical changes observed; dopamine and GABA levels increased as the severity of signs of poisoning increased. These results clearly demonstrate that HI-6 can penetrate into the brain of control and soman-intoxicated animals. Tandem measurement of dopamine electrochemically and HI-6 by UV detection provides a simple method for obtaining data on HI-6 penetration into the brain in neurochemical studies of soman poisoning and its treatment.
Cassel
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GE
Department of NBC Defence, National Defence Research Establishment, Umeå, Sweden.
Fosbraey
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P
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D000931:Antidotes / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010091:Oximes; D011726:Pyridinium Compounds / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000506:poisoning*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000931:Antidotes; D018377:Neurotransmitter Agents; D010091:Oximes; D011726:Pyridinium Compounds; D005680:gamma-Aminobutyric Acid; D012999:Soman; D000110:Acetylcholinesterase; C022870:asoxime chloride; D004298:Dopamine