Comparative effects of phencynonate hydrochloride and scopolamine hydrobromide against organophosphorus nerve-agent induced seizure activity and neuropathology
Abstract
This study utilized the guinea pig NA-seizure model to assess and compare the effectiveness of phencynonate hydrochloride (PCH), a compound that possesses both anticholinergic and anti-N-methyl-D-aspartate activities, and of scopolamine hydrobromide (SCP), a purely anti-muscarinic compound, when given at the early (at time of seizure onset) or late (40 min after seizure onset) phase of seizure progression. Administered at seizure onset, PCH and SCP were both effective at terminating seizure activity against all NAs, with ED50 values for SCP generally lower. At the 40 min treatment time, ED50 values were obtained following GA, GD, GF, and VR challenges for SCP, but for PCH values could only be obtained following GD, indicating a superior efficacy of SCP. When seizure activity was controlled, a significant improvement in weight loss, neuropathology, and survival was observed, regardless of treatment or NA challenge. These results demonstrate the differing efficacies of these two similarly structured anticholinergic compounds with delayed administration and warrant further investigation into the timing and mechanisms of the seizure maintenance phase in different animal model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 24, 2018
- Accession Number
- AD1060790
Entities
People
- Cindy Acon-chen
- Jeffrey A. Koenig
- Tsung-Ming Shih
Organizations
- United States Army Medical Research Institute of Chemical Defense