HI-6 and TMB-4 were the most effective and safe of 7 cholinesterase reactivators tested as agents for the prophylaxis of proserine poisoning of male mice. The reactivator HI-6 strongly potentiated the prophylactic efficacy of a mixture of atropine and arpenal administered in the doses sufficient for the blockade of both the m- and h-cholinoreactive systems of mice. As demonstrated by experiments in vitro, HI-6 and TMB-4 did not reacivate proserine-inhibited cholinesterase. The natural anticholinesterase activity of HI-6 was negligible. Based on the correlation of the data obtained to the reported data indicating that HI-6 has a low ganglioblocking activity it is inferred that the direct effect on the receptor is of no importance for the potentiating effect. It is assumed that HI-6 modulates the cholinoreactive systems, which leads to a dramatic increase of the efficacy of cholinolytics.
Download full-text PDF |
Source |
---|
Int J Mol Sci
November 2024
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.
Drug Discov Today
December 2024
Tunneling Group, Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland. Electronic address:
The main function of acetylcholinesterase (AChE) is to regulate the levels of one of the most important neurotransmitters: acetylcholine. This makes AChE an ideal molecular target for the treatment of neurodegenerative diseases and dementia (such as Alzheimer's disease), as well as for the neutralisation of natural toxins (e.g.
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 PDFPDA J Pharm Sci Technol
October 2024
Israel Defense Forces (IDF), Medical Corps, Pharmacy, Biomedical Engineering & Medical Supplies Branch, Israel; and.
Obidoxime chloride is an antidote for nerve gas intoxication. As an emergency medicine, it is being stored by the Israel Defense Forces (IDF) scattered throughout Israel in depots without a controlled environment (field conditions), thus being exposed to high and fluctuating temperatures. These conditions do not meet the manufacturer's requirements.
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.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!