Hypothermia: limited tolerance to repeated soman administration and cross-tolerance to oxotremorine.
The effect of repeated administration of the organophosphate anticholinesterases, soman (pinacolyl methylphosphonofluoridate) and DFP (diisopropylfluorophosphate) on core temperature was investigated in mice. Mice were implanted with telemetry transmitters for the monitoring of core temperature. Following repeated administration of soman (3-10 injections), tolerance (as defined by a decrease in the organophosphate-induced hypothermia upon subsequent administration) to the organophosphate-induced hypothermia was evident after the 5th injection; however, there was cross-tolerance to oxotremorine hypothermia as early as after the 3rd injection of soman. Following repeated administration of DFP, there was no tolerance to the DFP-induced hypothermia following 5 injections, whereas cross-tolerance to oxotremorine was evident following the 5th injection. The organophosphate-induced hypothermia may have another component which contributes to the response. It is proposed that the cross-tolerance to oxotremorine hypothermia after subchronic administration of an anticholinesterase is representative of the functionality of muscarinic cholinergic receptor coupling.
Clement
J G
JG
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007531:Isoflurophate / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology*; D012999:Soman / Q000494:pharmacology*
D007531:Isoflurophate; D010095:Oxotremorine; D012999:Soman; D006899:Mixed Function Oxygenases; D002265:Carboxylic Ester Hydrolases; D000110:Acetylcholinesterase