Pharmacological nature of soman-induced hypothermia in mice.
The object of the study was to determine the pharmacological nature of pinacolyl methylphosphonofluoridate (soman)-induced hypothermia in mice. This was accomplished by examining the soman hypothermia dose response and the effect of various pharmacological antagonists in comparison to the hypothermia responses of muscarinic and nicotinic cholinergic agonists such as oxotremorine and nicotine and another anticholinesterase, physostigmine. Core temperature in mice was monitored by telemetry. In general, atropine antagonized oxotremorine, physostigmine, and soman hypothermia but not nicotine hypothermia whereas mecamylamine antagonized nicotine hypothermia but not that produced by the other agonists. Soman hypothermia was not affected significantly by various pharmacological antagonists, suggesting that other neurotransmitters were not involved in the expression of soman hypothermia. Soman hypothermia appears to be due to muscarinic receptor stimulation and can be effectively antagonized, but not completely, by the use of atropine. Acetylcholinesterase oxime reactivators, such as HI-6 and toxogonin, were ineffective in antagonizing soman-induced hypothermia and reactivating hypothalamic acetylcholinesterase, whereas HI-6 was effective in reactivating soman-inhibited diaphragm acetylcholinesterase when administered up to 10 min after soman, indicating that aging of the soman-inhibited acetylcholinesterase had not occurred. Soman hypothermia appears to be primarily a muscarinic receptor-related event.
Clement
J G
JG
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alta, Canada.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009768:Obidoxime Chloride / Q000494:pharmacology; D010091:Oximes; D010095:Oxotremorine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010830:Physostigmine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D012999:Soman / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D010095:Oxotremorine; D008464:Mecamylamine; D009538:Nicotine; D001285:Atropine; D012999:Soman; D010830:Physostigmine; D000110:Acetylcholinesterase; C022870:asoxime chloride