Hormone- and dose schedule-dependent protection by HI-6 against soman and tabun poisoning.
The protective ratio produced by HI-6 (with atropine) against soman and tabun poisoning in rats and guinea pigs was determined. The amount of protection afforded by HI-6 decreased with time following poisoning, prompting us to examine the effects of repeated doses of HI-6 (four additional) given over a 5-hr period. In addition, it was determined that HI-6 produced much better protection in female rats than male rats, which led to a study of the hormone dependence of this activity. When in addition to the first dose of HI-6 four additional doses were given over a 5-hr period, the protective ratio, defined as LD50 in treated animals/LD50 in untreated animals, in males against soman, increased from 4.2 to 7.8, and against tabun, from 2.5 to 6.6. A single dose of HI-6 produced a protective ratio in females of 10.5 against soman and 4.3 against tabun, whereas multiple doses increased these values to greater than 27 and 22, respectively. A regimen consisting of gonad removal and long-term treatment with a sex hormone of the opposite gender reversed the sex-related differences in response to the protective effects of HI-6. In addition a single injection of HI-6 (plus atropine), 1 min following either soman or tabun, produced good protective ratios in guinea pigs against both soman (between 4 and 5) and tabun (5.1); however, there was no apparent hormone-dependent effect similar to that obtained in rats. The results demonstrate unequivocal protective effects of HI-6 against tabun and a very dramatic hormone-dependent factor in its activity against either organophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
Lundy
P M
PM
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada.
Goulet
J C
JC
Hand
B T
BT
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D009768:Obidoxime Chloride / Q000494:pharmacology; D009919:Orchiectomy; D010755:Organophosphates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors*; D010052:Ovariectomy; D010091:Oximes; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013045:Species Specificity; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D013739:Testosterone; D012999:Soman; C022870:asoxime chloride; C009374:tabun