Green P G, Kitchen I, Crowder M
Department of Biochemistry, University of Surrey, Guildford.
Neurotoxicol Teratol. 1988 Jul-Aug;10(4):315-9. doi: 10.1016/0892-0362(88)90033-5.
Interactions between anticholinesterases and opioid drugs on antinociception and locomotor behaviour have been studied in the mouse. The anticholinesterase di-isopropylfluorophosphate (DFP) (1 mg/kg), pyridostigmine (1 mg/kg) and neostigmine (200 micrograms/kg) or drugs used to treat anticholinesterase poisoning (atropine, pralidoxime and diazepam) were not antinociceptive. DFP, at doses which produced marked neurotoxicity (2 mg/kg), produced antinociception which was not mediated by opioid receptors. The antinociceptive effects of alfentanil, but not fentanyl or morphine, were potentiated by DFP, whereas pyridostigmine and neostigmine were without effect. The potentiating activity of DFP was unaffected by atropine, pralidoxime and diazepam. DFP (1 mg/kg) produced a small degree of hypolocomotion whilst atropine and pralidoxime produced marked hyperlocomotion. Diazepam alone and with DFP, atropine, pralidoxime or opioid drugs produced marked motor incapacitation. Hyperlocomotion induced by morphine and alfentanil was reduced by DFP but fentanyl hyperlocomotion was unaffected. Treatment of DFP toxicity with atropine and pralidoxime reversed the effects on alfentanil locomotion but failed to alter DFP's action upon morphine or fentanyl locomotion. Atropine and pralidoxime treatment alone did not affect fentanyl hyperlocomotion, attenuated alfentanil hyperlocomotion and produced marked hypolocomotion in morphine-treated mice. Opioids and anticholinesterases do not exhibit common interactions and their effects are dependent on both opioid, anticholinesterase and the behaviour studied.
已在小鼠中研究了抗胆碱酯酶与阿片类药物在镇痛和运动行为方面的相互作用。抗胆碱酯酶二异丙基氟磷酸酯（DFP）（1毫克/千克）、吡啶斯的明（1毫克/千克）和新斯的明（200微克/千克）或用于治疗抗胆碱酯酶中毒的药物（阿托品、解磷定和地西泮）均无镇痛作用。DFP在产生明显神经毒性的剂量（2毫克/千克）下产生的镇痛作用不是由阿片受体介导的。阿芬太尼的镇痛作用可被DFP增强，而芬太尼或吗啡则无此作用，而吡啶斯的明和新斯的明则无影响。DFP的增强活性不受阿托品、解磷定和地西泮的影响。DFP（1毫克/千克）产生轻度运动减少，而阿托品和解磷定则产生明显的运动增多。单独使用地西泮以及与DFP、阿托品、解磷定或阿片类药物联合使用时，会产生明显的运动失能。吗啡和阿芬太尼引起的运动增多可被DFP降低，但芬太尼引起的运动增多不受影响。用阿托品和解磷定治疗DFP毒性可逆转对阿芬太尼运动的影响，但未能改变DFP对吗啡或芬太尼运动的作用。单独使用阿托品和解磷定治疗不影响芬太尼引起的运动增多，减弱阿芬太尼引起的运动增多，并在吗啡治疗小鼠中产生明显的运动减少。阿片类药物和抗胆碱酯酶不表现出共同的相互作用，它们的作用取决于阿片类药物、抗胆碱酯酶以及所研究的行为。
