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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/1056-8719(96)00027-5 | DOI Listing |
Exp Neurol
December 2024
Neuroscience Department, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, MD, United States of America. Electronic address:
Exposure to organophosphorus nerve agents irreversibly inhibits acetylcholinesterase and may lead to cholinergic crisis and seizures. Although benzodiazepines are the standard of care after nerve agent-induced status epilepticus, when treatment is delayed for up to 30 min or more, refractory status epilepticus can develop. Adult male rodents are often utilized for evaluation of therapeutic efficacy against nerve agent exposure.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
December 2024
United States Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, USA. Electronic address:
Chemical warfare nerve agents (CWNAs) are potent and irreversible inhibitors of acetylcholinesterase (AChE). Oxime reactivators are an important part of the standard treatment for CWNA exposure as they can reactivate inhibited AChE. Evaluating the oxime candidates of interest in biological samples requires analytical detection methods and oxime reactivators as a class of compounds have historically been notoriously difficult to isolate, detect and analyze in an analytical laboratory, and there are currently no sensitive or robust analytical detection methods in the literature.
View Article and Find Full Text PDFBioorg Chem
December 2024
University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic; University Hospital in Hradec Kralove, Biomedical Research Centre, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. Electronic address:
Mono-quaternary pyridinium oximes derived from K-oximes K027, K048 and K203 were designed, synthesized and evaluated for the reactivation of organophosphate-inhibited cholinesterases. The incorporation of the halogen atoms to the structure decreased the pK value of the oxime group resulting in an increased formation of oximate necessary for reactivation. The stability and pK values were found to be similar to analogous bis-quaternary compounds.
View Article and Find Full Text PDFJ Toxicol Environ Health A
December 2024
Interdisciplinary Center for Biotechnology Research, Federal University of Pampa, São Gabriel, Brazil.
ACS Appl Mater Interfaces
September 2024
State Key Laboratory of National Security Specially Needed Medicines, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P. R. China.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!