Soman and sarin induce a long-lasting naloxone-reversible analgesia in mice.
Soman (50 micrograms/kg) and sarin (120 micrograms/kg), potent organophosphate anticholinesterase agents, produced an analgesic response in the mouse hotplate latency test. Naloxone antagonized but did not completely reverse the soman- and sarin-induced analgesia, whereas atropine antagonized completely the soman-and sarin-induced analgesia. Soman poisoning did not potentiate morphine-induced analgesia. It was simply an additive response. In survivors of soman (287 micrograms/kg) poisoning, the analgesia was more pronounced and was still apparent 96 hr after administration. This analgesia was completely antagonized by naloxone. Similar results were found in survivors of sarin (510 micrograms/kg) poisoning. The organophosphate-induced analgesia was not due to physical incapacitation as evidenced by performance on the accelerating rotorod. It is suggested that the organophosphate-induced analgesia is due to a combination of an increased concentration of acetylcholine due to inhibition of acetylcholinesterase combined with a reduced destruction of endogenous opioid-like substances due to organophosphate inhibition of proteases.
D000700:Analgesics; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011930:Reaction Time; D012524:Sarin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012999:Soman / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000700:Analgesics; D009943:Organophosphorus Compounds; D009270:Naloxone; D001285:Atropine; D012999:Soman; D012524:Sarin