Blockade of acetylcholine synthesis in organophosphate poisoning.
In spite of worldwide research efforts in the search for the treatment of organophosphate poisoning, the substances with practical antidotal capabilities remain to be discovered. This problem has generally been approached by attempting to reactivate the inhibited acetylcholinesterase. Our approach consisted of reducing the amount of the lethal agent acetylcholine by blocking its synthesizing enzyme cholineacetylase with methyl methane thiol sulfonate (MMTS). We have taken into consideration that we are dealing with acute toxicological problems. This applies for poisoning as well as for treatment, and therefore in the present stage we can only present minimal results. The time from sarin (2 mg/kg) injection to death in rats (controls) was 2:59 min. With a MMTS dosage of 133.5 mg/kg prior to sarin, it was prolonged to 20:55 min (p less than 0.01). With the same dosage of MMTS under identical conditions, the time from soman (2 mg/kg) injection to death was prolonged from 6:08 to 14:48 min (p less than 0.01). Although MMTS cannot be used as a therapeutic agent, our attempt has demonstrated a utility in treating organophosphate poisoning in mice and rats and points in a direction where further work might be fruitful.
D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D004347:Drug Interactions; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D008741:Methyl Methanesulfonate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D012524:Sarin / Q000633:toxicity*; D012999:Soman / Q000633:toxicity; D013997:Time Factors
D009943:Organophosphorus Compounds; C014674:methyl methanethiosulfonate; D012999:Soman; D008741:Methyl Methanesulfonate; D012524:Sarin; D000109:Acetylcholine