Cage Convulsants and Anticonvulsants
Abstract
The interactions of organophosphorus compounds with gamma aminobutyric acid (GABA)-ergic neurous have been studied by the specific binding of the cage convulsant, t-butylbicyclophosphorothionate (TBPS). Scratchard analysis of labled TBPS binding to cortical membranes from adult rat and chicken brain yielded two binding constants (Kd = 1 nM and 200 nM). The anticonvulsants etomidate and etazolate were potent displacers of TBPS. Secobarbital was moderatly effective, while phenobarbital and diazepam were poor displacers. Organophosphorus insecticides, such as O-ethyl-O-p-nitrophenyl phenylthiophosphonate (EPN), paraoxon, and Dyfonate, were moderately effective displacers of TBPS binding. The interaction of organophosphorus cage convulsants with GABA-gates chloride channels was studied by flux measurements in heurous cultured from the chick embryo cerebrum. TBPS proved to be a potent inhibitor of GABA-dependent C1 uptake. These results indicate that TBPS acts as a GABA antagonist via direct blockade of neurone C1 channels. Thus the convulsive effects of cage compounds and perhaps other organophosphorus compounds may be exerted by interference with GABAergic rather than cholinergic neurotransmission.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 31, 1985
- Accession Number
- ADA182134
Entities
People
- Eugene M. Barnes Jr.
Organizations
- Baylor College of Medicine