The evaluation of prophylactic efficacy of newly developed reversible inhibitors of acetylcholinesterase in soman-poisoned mice - a comparison with commonly used pyridostigmine.

Basic Clin Pharmacol Toxicol

Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.

Published: December 2014

The ability of four newly developed reversible inhibitors of acetylcholinesterase (PC-37, PC-48, JaKo 39, JaKo 40) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated and compared. No reversible inhibitor of acetylcholinesterase studied was able to decrease the LD50 value of soman in mice. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of acetylcholinesterase was not able to significantly protect mice against soman-induced lethal acute toxicity. In addition, neither pyridostigmine nor new reversible inhibitors of acetylcholinesterase was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of acetylcholinesterase is not promising.

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcpt.12269DOI Listing

Publication Analysis

Top Keywords

inhibitors acetylcholinesterase
20
reversible inhibitors
16
soman-poisoned mice
16
newly developed
8
developed reversible
8
efficacy antidotal
8
antidotal treatment
8
pharmacological pre-treatment
8
mice
7
acetylcholinesterase
6

Similar Publications

The abnormal expression of acetylcholinesterase (AChE) is linked to the development of various diseases. Accurate determination of AChE activity as well as screening AChE inhibitors (AChEIs) holds paramount importance for early diagnosis and treatment of AChE-related diseases. Herein, a fluorescent and colorimetric dual-channel probe based on gold nanoclusters (AuNCs) and manganese dioxide nanosheets (MnO NSs) was developed.

View Article and Find Full Text PDF

In this work, artificial neural network coupled with multi-objective genetic algorithm (ANN-NSGA-II) has been used to develop a model and optimize the conditions for the extracting of the Mentha longifolia (L.) L. plant.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is primarily caused by oxidative stress, hyperphosphorylated τ-protein aggregation, and amyloid-β deposition. Changes in dopaminergic and serotoninergic neurotransmitter pathways are linked to certain symptoms of AD. Derivatives of bicyclic and tricyclic cyclohepta[b]thiophene were developed to identify new potential candidates as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the treatment of AD.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases of dementia. Although the exact pathophysiological causes of AD remain unclear, its pathogenesis is primarily driven by several distinct biochemical alterations: (i) the accumulation of toxic Aβ plaques, (ii) the hyperphosphorylation of tau proteins, (iii) oxidative stress resulting in cell death, and (iv) an imbalance between the two main neurotransmitters, glutamate and acetylcholine (ACh). Currently, there are very few medications available and no treatment.

View Article and Find Full Text PDF

Quinazoline derivatives as novel bacterial sphingomyelinase enzyme inhibitors.

Bioorg Chem

December 2024

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Ankara, Türkiye. Electronic address:

Bacillus cereus sphingomyelinase C (B. cereus SMase), which plays a crucial role in bacterial virulence, has emerged as a new therapeutic target for treating opportunistic infections caused by this pathogen. It also shares catalytic domain similarity with human neutral sphingomyelinase 2 (nSMase2), which is implicated in Alzheimer's disease.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!