Clement J G
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alta, Canada.
Pharmacol Biochem Behav. 1993 Mar;44(3):689-702. doi: 10.1016/0091-3057(93)90187-x.
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.
本研究的目的是确定甲基膦酸频那酯（梭曼）诱导的小鼠体温过低的药理学性质。这是通过检查梭曼低温剂量反应以及各种药理学拮抗剂的作用，并与毒蕈碱和烟碱胆碱能激动剂（如震颤素和尼古丁）以及另一种抗胆碱酯酶药物毒扁豆碱的低温反应进行比较来实现的。通过遥测技术监测小鼠的核心体温。一般来说，阿托品可拮抗震颤素、毒扁豆碱和梭曼引起的体温过低，但不能拮抗尼古丁引起的体温过低，而美加明可拮抗尼古丁引起的体温过低，但不能拮抗其他激动剂引起的体温过低。各种药理学拮抗剂对梭曼引起的体温过低没有显著影响，这表明其他神经递质不参与梭曼引起的体温过低的表现。梭曼引起的体温过低似乎是由于毒蕈碱受体刺激所致，使用阿托品可有效拮抗，但不能完全拮抗。乙酰胆碱酯酶肟类复活剂，如HI-6和氯磷定，在拮抗梭曼诱导的体温过低和使下丘脑乙酰胆碱酯酶复活方面无效，而HI-6在梭曼给药后10分钟内给药时，可有效使梭曼抑制的膈肌乙酰胆碱酯酶复活，这表明梭曼抑制的乙酰胆碱酯酶尚未老化。梭曼引起的体温过低似乎主要是一个与毒蕈碱受体相关的事件。
