Efficacy of HI-6 and HLÖ-7 in preventing incapacitation following nerve agent poisoning

article


Melchers, B.P.C.

Philippens, I.H.C.H.M.

Wolthuis, O.L.
The therapeutic efficacy of the oximes HI-6 and HLo-7 (132.5 μmol/kg), in combination with atropine, in soman- or tabun-intoxicated guinea pigs was compared, particularly with respect to recovery of shuttlebox performance and electroencephalograms (EEGs). After 1.5 x LD50 soman SC, therapy with HI-6 or HLo-7 resulted in survival of 87.5% of the animals in each group. In both groups postintoxication performance decrements and EEG abnormalities lasted approximately 2 weeks after intoxication. After 3 x LD50 soman all HLo-7-treated animals died within 5 h; 70% of the HI-6-treated animals were still alive after 8 h; however, only 10% survived more than 24 h. After 2 x LD50 tabun 36% of the HI-6-treated animals died; HLo-7 prevented lethality and led to faster recovery of performance and EEG than after HI-6. Even after 7.5 x LD50 tabun, followed by HLo-7, full recovery was reached within 1 week in the surviving animals (82%). In soman-intoxicated guinea pigs HI-6 is therapeutically slightly more effective than HLo-7. HLo-7 is far more effective, under similar conditions, against tabun intoxication than HI-6.
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Behavioral performanceEEGPostintoxication incapacitation1 (4 carbamoylpyridinio) 1' (2 hydroxyiminomethylpyridinio)dimethyl ether1 [2,4 bis(hydroxyiminomethyl)pyridinio] 1' (4 carbamoylpyridinio)dimethyl ether diiodideAtropineNerve gasOxime derivativeAnimal experimentControlled studyDrug efficacyElectroencephalogramGuinea pigIntoxicationIntramuscular drug administrationLethalityNonhumanPerformanceSurvival rateAnimalBehavior, AnimalChemical warfare agentsCholinesterase inhibitorsCholinesterase reactivatorsConditioning, OperantElectroencephalographyGuinea pigsLethal dose 50PyridinesPyridinium compoundsRespiratory mechanicsAnimaliaCaviaCavia porcellusSus scrofaNutritionAtropine, 51-55-8HI 6, 34433-31-3HLo 7, 120103-35-7Phosphoric acid estersSoman, 96-64-0Tabun, 77-81-6
TNO Identifier
82282
Repository link
https://resolver.tno.nl/uuid:b7b6a2a8-4e08-4805-ad60-f4c75abb99d8
ISSN
00913057
Source
Pharmacology, Biochemistry and Behaviour, 49(4), pp. 781-788.
Pages
781-788
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