Print Email Facebook Twitter Therapy of organophosphate poisoning in the rat by direct effects of oximes unrelated to ChE reactivation Title Therapy of organophosphate poisoning in the rat by direct effects of oximes unrelated to ChE reactivation Author van Helden, H.P.M. de Lange, J. Busker, R.W. Melchers, B.P.C. Medisch Biologisch Laboratorium TNO Publication year 1991 Abstract Isolated rat diaphragm preparations treated with soman or with the irreversible and oxime resistant cholinesterase (ChE) inhibitor S27 (see Compounds) showed a considerable recovery of neuromuscular transmission (NMT) during incubation with the (bis)pyridinium oximes HI-6, HGG-12, P2S and obidoxime. In the soman-treated preparations this NMT recovery was predominantly caused by reactivation of acetylcholinesterase (AChE) but in the S27-treated preparations it was caused by a direct (pharmacological) effect unrelated to enzyme reactivation. Atropinized rats were artificially ventilated after injection with 3 x LD50 soman for 3 h and then treated with HI-6, i.e. at a time when oxime reactivation of soman inhibited ChE is no longer possible. Nevertheless, these rats started to breathe spontaneously and 50-60% survived more than 24 h, whereas all control animals (saline instead of HI-6) died within 10 min after artificial ventilation was terminated. In such animals no significant reactivation of ChE activity at various time intervals followed HI-6 treatment was found, either in the diaphragms or in the brains. There was a significant amount of NMT (50%) in vitro in diaphragms obtained from these animals. This NMT did not improve in vitro in the presence of HI-6 and was not inhibited by soman administered to the medium. It is concluded that in this case the NMT found was based on synaptic adaptation to the continued inhibition of ChE and that the survival of the animals might be due to a combination of this synaptic adaptation and central direct effects of HI-6. Chemicals/CAS: Antidotes; Cholinesterase Reactivators; HGG 12, 83972-73-0; HI 6, 34433-31-3; Obidoxime Chloride, 114-90-9; Organophosphorus Compounds; Oximes; Pralidoxime Compounds; pralidoxime, 6735-59-7; Pyridinium Compounds Subject BiologyAcetylcholinesteraseDirect effectHGG-12HI-6ObidoximeOrganophosphate poisoningP2S1 (4 carbamoylpyridinio) 1' (2 hydroxyiminomethylpyridinio)dimethyl ether[(3 benzoyl 1 pyridiniomethyl) (2 hydroxyiminomethyl 1 pyridiniomethyl)] etherObidoximeOrganophosphateOximeSomanAnimal experimentAnimal tissueDiaphragmEnzyme inhibitionEnzyme reactivationIntravenous drug administrationMaleNonhumanPriority journalRatAnimalAntidotesBlood-Brain BarrierCholinesterase ReactivatorsDiaphragmIn VitroMaleNeuromuscular JunctionObidoxime ChlorideOrganophosphorus CompoundsOximesPralidoxime CompoundsPyridinium CompoundsRatsRespiratory InsufficiencySynaptic TransmissionAnimalia To reference this document use: http://resolver.tudelft.nl/uuid:f1345827-3dc7-4b4b-84b0-09655086d63c TNO identifier 231594 ISSN 0340-5761 Source Archives of Toxicology, 65 (7), 586-593 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.