Pharmacology of Adenosine A₁ Receptor Agonist in a Humanized Esterase Mouse Seizure Model Following Soman Intoxication.

ABSTRACT: Recently a novel genetically modified mouse strain with serum carboxylesterase knocked-out and the human acetylcholinesterase gene knocked-in (KIKO) was created to simulate human responses to nerve agent (NA) exposure and its standard medical treatment. A₁ adenosine receptor (A₁AR) agonist N-bicyclo-(2.2.1)-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone is a potent anticonvulsant and neuroprotectant (A/N) in both rat and KIKO mouse soman (GD) seizure models. In this study we utilized the KIKO mouse to evaluate further the basic pharmacologic A/N effects of ENBA as an adjunct to standard NA medical treatments (i.e., atropine sulfate, pralidoxime chloride [2-PAM], and midazolam). Male mice, implanted with cortical electroencephalographic (EEG) electrodes, were pretr

SUBMITTER: Shih TM 

PROVIDER: S-EPMC11374867 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature