COMPARISON OF SEVERAL OXIMES ON REACTIVATION OF SOMAN-INHIBITED BLOOD, BRAIN AND TISSUE CHOLINESTERASE ACTIVITY IN RATS

The ability of three oximes, HI-6, MMB-4 and ICD-467, to reactivate ch olinesterase (ChE) inhibited by the organophosphorus compound soman wa s compared in blood (plasma and erythrocytes), brain regions (includin g spinal cord) and peripheral tissues of rats. Animals were intoxicate d with soman (100 mug/kg, SC; equivalent to 0.9 x LD50 dose) and treat ed 1 min later with one of these oximes (100 or 200 mumol/kg, IM). Tox ic sign scores and total tissue ChE activities were determined 30 min later. Soman markedly inhibited ChE activity in blood (93-96%), brain regions (ranging from 78% to 95%), and all peripheral tissues (ranging from 48.9% to 99.8%) except liver (11.9%). In blood, treatment with H I-6 or ICD-467 resulted in significant reactivation of soman-inhibited ChE. In contrast, MMB-4 was completely ineffective. HI-6 and ICD-467 were equally effective at the high dose. At the low dose ICD-467 treat ment resulted in significantly higher plasma ChE than HI-6 treatment, whereas HI-6 treatment resulted in higher erythrocyte ChE than ICD-467 treatment. However, none of these three oximes reactivated or protect ed soman-inhibited ChE in the brain. In all peripheral tissues (except liver) studied, MMB-4 was not effective. HI-6 reactivated soman-inhib ited ChE in all tissues except lung, heart, and skeletal muscle. ICD-4 67 was highly effective in reactivating ChE in all tissues and afforde d a complete recovery of ChE to control levels in intercostal muscle a nd salivary gland. Oxime treatments did not modify the toxic scores pr oduced by soman. However, treatment with the high dose (200 mumol/kg) of ICD467 depressed respiration and two of the six rats died in 10 min . These observations indicate that MMB-4 is completely ineffective in protecting and/or reactivating soman-inhibited ChE, HI-6 is an effecti ve ChE reactivator as reported earlier in rats and other species, and the imidazolium oxime ICD-467 is a powerful reactivator of somaninhibi ted ChE; however, its toxic interactions with soman may not be related to tissue ChE levels.