Abstract
A SERIES of bicyclic organophosphorus (PTBO) compounds (Fig. 1) described by Bellet and Casida1 were found to produce seizures and death within minutes of their injection into mice. In spite of the chemical resemblance of these substances to anticholinesterase agents, doses of the PTBO compounds many times those necessary to produce death had no effect on brain cholinesterase activity1, and the mechanism of their convulsant action remained obscure. We have, therefore, investigated the action of ethyl, isopropyl and pentyl PTBO compounds as putative antagonists both of the depressant action of γ-aminobutyrate (GABA) on single neurones in the rat brain and of the depolarising action of GABA on the isolated rat superior cervical ganglion. Our results suggest that the convulsant action of the PTBO compounds may be related to their ability to antagonise the actions of GABA released as an inhibitory neurotransmitter2 at synapses in the brain.
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BOWERY, N., COLLINS, J. & HILL, R. Bicyclic phosphorus esters that are potent convulsants and GABA antagonists. Nature 261, 601–603 (1976). https://doi.org/10.1038/261601a0
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DOI: https://doi.org/10.1038/261601a0
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