Intraperitoneal (IP) administration of the acetylcholinesterase inhibitor, soman (10-40 micrograms/kg), suppressed in a dose-related manner response rates in rats maintained under a multiple fixed-interval 50-s fixed-ratio 25 schedule of food delivery. Chronic administration of soman at weekly intervals resulted in tolerance to the response. When soman administration was separated by 2-5 weeks in individual rats, the suppressive effects of the agent again became apparent. Analysis of acetylcholinesterase activity revealed that enzyme inhibition was limited to gastrointestinal areas near the site of injection. There was no significant effect on brain acetylcholinesterase even following IP injection of doses which completely suppressed responding. The IP route may be useful for studying tolerance and other chronic effects of soman without producing generalized toxicity.
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Chem Biol Interact
January 2025
Department of Toxicology and Military Pharmacy, Military Faculty of Medicine, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic; Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove, Czech Republic. Electronic address:
The current pharmacological pretreatment and medical treatment of nerve agent poisoning is an insufficiently addressed medical task. The prophylactic efficacy of a novel compound acting dually as an acetylcholinesterase inhibitor and NMDA receptor antagonist (K1959) and the therapeutic efficacy of a novel NMDA receptor antagonist (K2060) were evaluated in the NMRI mice model of nerve agent poisoning by tabun, soman and sarin. Their added value to the standard antidotal treatment (a combination of oxime reactivator and atropine) was also analyzed.
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Department of Oral Maxillofacial Radiologist, Department of OMFS & DOS College of Medicine and Dentistry, Riyadh Elm University, Saudi Arabia.
J Pharm Biomed Anal
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Department of Chemistry, Biochemistry and Physics, South Dakota State University, Box 2202, Brookings, SD 57007, USA. Electronic address:
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View Article and Find Full Text PDFBMJ Paediatr Open
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School of Nursing and Midwifery, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
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