Chiou G C, Li B H
Department of Medical Pharmacology and Toxicology, Texas A&M University College of Medicine, College Station 77843-1114.
Life Sci. 1994;55(1):69-75. doi: 10.1016/0024-3205(94)90082-5.
In Vivo cardiovascular neuromuscular preparation of rats was used to study the prophylaxis and mechanism of diisopropyl fluorophosphate (DFP) intoxication by presynaptic cholinolytic agents (ganglionic blocking agents), including hexamethonium, trimethaphan and mecamylamine. The lethal action of DFP was partially or completely prevented by pretreatment of rats with hexamethonium (10 mg/kg), trimethaphan (80 mg/kg) and mecamylamine (30 mg/kg). Combined use of these drugs with 2-PAM (100 mg/kg) improved further the prophylaxis of DFP lethality. The mechanism of prophylaxis could be due to the reduction of acetylcholine turnover and accumulation at the synaptic cleft as hemicholinium prevented the DFP intoxication efficiently. In all cases, DFP caused cardiovascular suppression before neuromuscular blockade indicating that the cardiovascular system is much more sensitive than the neuromuscular junction to DFP intoxication.
采用大鼠体内心血管神经肌肉制备方法，研究包括六甲铵、曲美芬和美加明在内的突触前胆碱能分解剂（神经节阻断剂）对二异丙基氟磷酸酯（DFP）中毒的预防作用及其机制。用六甲铵（10毫克/千克）、曲美芬（80毫克/千克）和美加明（30毫克/千克）预处理大鼠，可部分或完全预防DFP的致死作用。这些药物与2-解磷定（100毫克/千克）联合使用，可进一步提高对DFP致死性的预防效果。预防机制可能是由于乙酰胆碱周转率降低以及在突触间隙的积累减少，因为半胱氨酸能有效预防DFP中毒。在所有情况下，DFP在神经肌肉阻断之前就引起心血管抑制，这表明心血管系统对DFP中毒比神经肌肉接头更敏感。
