Measurement of the oxime HI-6 after peripheral administration in tandem with neurotransmitter levels in striatal dialysates: Effects of soman intoxication

被引:30
作者
Cassel, GE [1 ]
Fosbraey, P [1 ]
机构
[1] CHEM & BIOL DEF ESTAB,DIV BIOL,SALISBURY SP4 0JQ,WILTS,ENGLAND
关键词
HI-6; rats; soman; HPLC; dopamine; GABA;
D O I
10.1016/1056-8719(96)00027-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu g/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.
引用
收藏
页码:159 / 166
页数:8
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