Therapeutic Effects Of Benthiactzine Against Intestinal Mucosa Barrier And Acid-base Disorder Induced By Cholinesterase Inhibitors

Medical scientists both civilian and military always pay close attention to the intoxication of cholinesterase inhibitors(ChEI). Intoxication of ChEI usually lead to MODS and MOF. Gastrointestinal tract is one of organs were directly influenced by ChEI. Intoxication of ChEI could give rise to functional disturbance of gastrointestinal mucosa barrier, simultaneous shift of bacterium and endotoxin, and directly or indirectly provoked to SIRS and MODS, which further evoke functional disturbance of gastrointestinal mucosa barrier. The muscarinic receptor antagonism as the treatment of the poisoning in clinic cause slow-moving gastrointestinal motility, aggravate the cholinesterase inhibitor poisoning, and cause enteroparalysis. Intoxication of ChEI could result in respiratory failure and circulatory failure, and induced disturbance of electrolyte and disequilibrium of acid base, and influenced the internal circumstance of organism, and resulted disturbance of cardiovascular system and central nerve system, and was the main reasons for death. So, there was an important significance to research the novel anti-cholinesterase.Our earlier studies showed that benthiactzine could antagonize against both M-receptors and N-receptors. It indicated that benthiactzine have a prior to antagonism blocking muscarinic acetylcholine receptors, but it is opposite to non-neuronal muscarinic acetylcholine receptor. This study shows that benthiactzine could protect the functional of gastrointestinal mucosa barrier, but antagonism is opposite. So we suppose that benthiactzine has a weaker affinity to M-receptors of intestinal mucosa and stomach intestine smooth muscle cell than antagonism. In earlier studies we found that benthiactzine could effectively against respiratory failure and circulatory failure induced by intoxication of ChEI. This study found that benthiactzine could improve and control mixed type acid poisoning of concomitant respiratory failure and circulatory failure. Basis theory of essay is follow:1. Effects of benthiactzine on functional disturbance of gastrointestinal mucosa barrier induced by ChEI. Male, weight 18-20g, KunMing mice, were used in the essay, and there were four groups, normal groups; VX groups; treatment of benthiactzine groups; antagonism groups; Xuebijing and anisodamine control groups especially. The VX groups were direct injected VX 0.02mg/kg, the groups were injected VX 0.02mg/kg after 10min injected medicine of treatment, and simultaneously injected Pralidoxime Chloride 10 mg/kg. The endotoxin of blood was detected by VX mice after 1.5h,3h,6h,24h,48h,72h. The results indicate that concentration of endotoxin in the blood was 5.36±1.62kEU/L after 1.5h in the normal groups, and was 11.47±3.90kEU/ml after 24h, and continually arised to 48h, reach at normal level after 72h. at 1.5h and 3h. concentration of endotoxin is visibly lower than model groups in benthiactzine groups, and reach at normal level at 48h. at the same condition, concentration of endotoxin is visibly higher than model groups in antagonism groups. This indicates that concentration of LPS decreased with increasing dose of benthiactzine injection during 1.5h-24h, but it is opposite in the group of treatment with antagonism, and there was a significant distinction.From these observations,it could be concluded: there was a serious damage to gastrointestinal tract mucous membrane by antagonism than benthiactzine, and the same consequence was caused by Xuebijing and anisodamine. So we can conclude that benthiactzine has a weaker affinity to M-receptors of gastrointestinal tract mucous membrane than antagonism.2. Effects of benthiactzine on mixed type acid poisoning of concomitant respiratory failure and circulatory failure induced by intoxiciation of ChEI. We investigate the changes of PaCO2, PO2, BE, BB, SB, CH+ after treatment with benthiactzine against the acid poisoning induced 1h by the cholinesterase inhibitor soman(2LD) in dog. The results indicate that PaCO2, PO2, BE, BB, SB, CH+ is 45.5±12.3mmHg, 87.8±14.3 mmHg, significant difference(p<0.01,n=7), -6.7±1.7mmol/L, 41.1±1.8mmol/L, 18.8±1.2mmol/L, 50.4±10.5mmol/L, especially, When it be continually treated above 6h, the life feature be recovered in the acid poisoning dog. when the acid poisoning induced 2h by the soman(4LD) in dog, the blood pressure decreased, MAP was below 45mmHg, and caused respiratory failure and circulatory failure. after treatment with benthiactzine 1h, PaCO2, CH+, PO2 changed to 40.2±7.9mmHg, 61.3±5.4mmol/L, 114.5±27.1mmHg,especially, The other symptoms has not been continuously worsened, and acid poisoning was partially controlled.From these observations,we come to conclusions as follow:The benthiactzine is a novel medicine of against acetylcholine M-receptors and N-receptors. In the earlier intoxiciation of cholinesterase inhibitors, benthiactzine could relieve the functional injury of gastrointestinal mucosa barrier induced by endotoxin in the blood. But antagonism could aggravate functional injury of gastrointestinal mucosa barrier, and further caused MODS.Intoxiciation of cholinesterase inhibitors could lead to compensated primary acute respiratory acid poisoning complicating continuous metabolic acid poisoning. After treatment with benthiactzine, the symptom of acid poisoning will be relieve, and break away from the acid poisoning state. Respiratory failure with circulatory failure in the organism caused to serious no-compensated primary chronicity respiratory acid poisoning complicating continuous metabolic and patient's condition was aggravated with increasing of time and dose. After treatment with benthiactzine, pH, PaCO2, PO2, CH+ have a significant change within one hour, the other symptoms have not continuously worsened, and acid poisoning was partially control.