Clement J G
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada.
Pharmacol Biochem Behav. 1991 Jun;39(2):305-12. doi: 10.1016/0091-3057(91)90184-4.
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.
研究了有机磷酸酯类抗胆碱酯酶药物梭曼（频哪基甲基膦酰氟）和二异丙基氟磷酸酯（DFP）反复给药对小鼠核心体温的影响。给小鼠植入遥测发射器以监测核心体温。反复给予梭曼（3 - 10次注射）后，在第5次注射后，对有机磷酸酯诱导的体温过低产生了耐受性（定义为随后给药时有机磷酸酯诱导的体温过低有所降低）；然而，早在第3次注射梭曼后，对氧化震颤素诱导的体温过低就出现了交叉耐受性。反复给予DFP后，5次注射后对DFP诱导的体温过低没有耐受性，而在第5次注射后对氧化震颤素的交叉耐受性明显。有机磷酸酯诱导的体温过低可能还有另一个促成该反应的成分。有人提出，抗胆碱酯酶亚慢性给药后对氧化震颤素诱导的体温过低的交叉耐受性代表了毒蕈碱胆碱能受体偶联的功能。
