Pharmacological Profile of CEB-1957 and Atropine toward Brain Muscarinic Receptors and Comparative Study of Their Efficacy against Sarin Poisoning

This study consists of two parts, first to compare the pharmacological profile of atropine and CEB-1957 substance toward muscarinic receptor subtypes. In various rat brain structures, binding properties were determined by competition experiments of [³H]pirenzepine, [³H]AF-DX 384, and [³H]4-DAMP in quantitative autoradiography of M1, M2, and M3 muscarinic receptor subtypes, respectively. Competition curves have shown that atropine presents similar nanomolar inhibition constants toward each subtype, while CEB-1957 has distinct affinities (K_ifrom 0.26 to 73 nM) with the following range order: M3 ≥ M2 > M1. The second part is to compare atropine and CEB-1957 (in combination with pralidoxime) for their ability to protect against the lethality induced by 2 × LD50 of the acetylcholinesterase inhibitor sarin. CEB-1957 reduced the mortality at doses 10 times lower than atropine. Finally, from these results, it is proposed that a selective blockade of M2 and M3 receptor subtypes could play a pivotal role in the protective effect against sarin poisoning.     

东莨菪碱治疗有机磷中毒阿托品依赖

目的 分析东莨菪碱辅助治疗有机磷农药中毒阿托品依赖现象的临床效果。方法 48例阿托品依赖患者在阿托品维持治疗量的基础上，应用东莨菪碱每次0．3—1．5mg,q4h-q8h静脉注射，症状消失后，与阿托品维持量交替注射，并逐渐减量。结果 全部病例阿托品依赖症状消失，采取交替注射减量、延长时间相结合逐渐减少或停用阿托品及东莨菪碱，直至病人痊愈。结论 东莨菪碱佐治阿托品依赖症状，疗效好，其抗毒蕈碱祥(M)作用，抑制腺体分泌的作用比阿托品强，可快速达阿托品化，使病程缩短，减少了阿托品用量，避免了阿托品中毒，对中枢N受体也具有作用，可弥补阿托品控制N祥症状的不足，而对大脑皮层呈普遍的抑制，具有镇静作用，较少出现狂躁，谵妄等中毒症状，值得临床推广应用。     

盐酸戊乙奎醚联合阿托品与单纯使用阿托品治疗重度急性有机磷中毒的临床疗效对比

目的：评价盐酸戊乙奎醚联合阿托品与单纯使用阿托品治疗重度急性有机磷中毒的临床疗效,探讨其临床适用性。方法病例选择从2013年5月至2014年4月于我院就诊的74例重度急性有机磷中毒患者。简单随机分为试验组37例和对照组37例,对照组患者给予单纯阿托品救治,试验组患者给予戊乙奎醚联合阿托品治疗。观察两组患者的阿托品总使用量,临床治愈疗效情况,观察两组患者胆碱酯酶活力恢复时间、中毒症状消失时间、平均住院时间和不良反应发生情况。结果试验组患者的阿托品总使用量为9．44±5．12mg,对照组患者阿托品总使用量为29．83±6．27mg,差异有统计学意义（t＝15．322,P＝0．000）;试验组患者治愈率为97．30％（36／37）,对照组患者治愈率为94．59％（35／37）,差异无统计学意义（χ2＝0．35,P＝0．5556）。试验组胆碱酯酶活力恢复时间、中毒症状消失时间和平均住院时间均明显低于对照组患者（ P ＜0．05）;试验组患者的相关不良反应发生比率低于对照组患者（P＜0．05）。结论盐酸戊乙奎醚联合阿托品治疗重度急性有机磷中毒患者的临床疗效显著,通过降低阿托品的使用剂量,也减少不良反应的发生,适合临床长期推广应用。     

Efficacy of Mono- and Bis-Pyridinium Oximes Versus Soman, Sarin and Tabun Poisoning in Mice

Efficacy of Mono- and Bis-Pyridinium Oximes Versus Soman, Sarinand Tabun Poisoning in Mice. Clement, J.G. (1983). Fundam. Appl.Toxicol. 3:533–535. Various oximes (PAM, toxogonin, TMB-4,HS-6, HI-6, HGG-12, HGG-42) combined with atropine were comparedas antidotes of soman, sarin and tabun poisoning in non-fastedCD-1^® male mice. TMB-4 was the most toxic oxime with ani.p. LD₅₀ value of 80 mg/kg and HI-6 was the least toxic oximewith an i.p. LD₅₀ of 588 mg/kg. Upon comparing ED₅₀ values,HGG-42 was the most effective oxime versus soman and tabun poisoningwhereas, HI-6 was the most effective oxime versus sarin poisoning.Further research needs to be done to explain the distinct differencesin efficacy of the oximes versus poisoning by soman, sarin ortabun.     

阿托品不同给药途径救治有机磷中毒的疗效对比研究

目的:探讨阿托品不同给药途径救治有机磷中毒的疗效.方法:选择我院2012年3月～2015年3月收治的78例急性有机磷农药中毒患者的临床资料进行回顾性分析,按给药途径分为两组,对照组患者先微量泵持续静脉输注阿托品,再行间歇静脉推注;观察组患者先行间歇静脉推注阿托品,达阿托品化后再采用微量泵持续静注.观察两组患者阿托品化时间、用量以及住院时间,比较两组临床治愈率和并发症发生率.结果:观察组的阿托品化时间、用量以及住院时间显著低于对照组;观察组患者的治愈率高达97.50％(39/40),并发症发生率低至7.50％(3/40),均显著优于对照组的81.58％(31/38)、34.21％(13/38),差异具有统计学意义(P＜0.05).结论:采用阿托品人工静脉推注,待患者阿托品化后再予以微量泵给药,不但起效速度快,临床疗效显著,而且并发症发生率低,值得在临床上推广.     

戊乙奎醚与阿托品治疗急性有机磷中毒的药物经济学分析

目的:评价戊乙奎醚与阿托品治疗急性有机磷农药中毒(AOPP)的经济性。方法:收集118例AOPP患者资料,按治疗方案的不同分为A组(59例)和B组(59例),其中A组轻度22例、中度20例、重度17例;B组轻度21例、中度21例、重度17例。在常规治疗的基础上,A组患者肌内注射盐酸戊乙奎醚注射液首次剂量1 mg(轻度)、2 mg(中度)、4 mg(重度),B组患者静脉注射硫酸阿托品注射液首次剂量2 mg(轻度)、5 mg(中度)、10 mg(重度),两组均视情况给予维持治疗待症状消失后停药。观察两组患者的临床疗效,乙酰胆碱酯酶恢复时间及不良反应发生情况。采用成本-效果分析方法评定两组轻、中、重度患者用药方案的经济性。结果:两组轻度中毒患者总有效率、乙酰胆碱酯酶恢复时间比较,差异均无统计学意义(P>0.05)。A组中、重度中毒患者总有效率均显著高于B组,乙酰胆碱酯酶恢复时间均显著短于B组,差异均有统计学意义(P<0.05)。两组轻、中、重度患者不良反应发生率比较,差异均无统计学意义(P>0.05)。轻度中毒患者,戊乙奎醚与阿托品的成本-效果比相当;中、重度中毒患者,戊乙奎醚的成本-效果比均显著低于阿托品。敏感度分析结果与一致。结论:在常规治疗的基础上,戊乙奎醚与阿托品治疗轻度AOPP患者的疗效、乙酰胆碱酯酶恢复时间均相当,对于中、重度AOPP患者戊乙奎醚在提高疗效、改善乙酰胆碱酯酶恢复时间方面均显著优于阿托品,且两种用药方案的安全性均较好。戊乙奎醚治疗中、重度AOPP患者具有成本效果优势。     

盐酸戊乙奎醚联合阿托品治疗有机磷农药中毒的应用

目的观察盐酸戊乙奎醚联合阿托品治疗急性有机磷农药中毒的临床疗效。方法 102例急性有机磷农药中毒的患者随机分为盐酸戊乙奎醚＋阿托品组和阿托品治疗组,两组同时给予氯解磷定治疗。结果盐酸戊乙奎醚＋阿托品组与阿托品治疗组比较,在中毒症状消失时间、阿托品化时间、恢复时间、血胆碱脂酶恢复时间、平均住院天数上均有显著性差异。盐酸戊乙奎醚＋阿托品组不良反应较阿托品治疗组明显减少。结论盐酸戊乙奎醚联合阿托品救治急性有机磷农药中毒副作用少、疗效高、安全可靠。     

Dose-Response Effects of Atropine and Hi-6 Treatment of Organophosphorus Poisoning in Guinea Pigs

ABSTRACT

HI-6 (1-2-hydroxyiminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino)-2-oxapropane dichloride) has been evaluated as an oxime alternative to pralidoxime, and toxogonin in the treatment of organophosphorus (OP) poisoning. The dose response effects of atropine (ATR) and HI-6 were investigated to more fully explore the interaction of these compounds in the treatment of OP poisoning. ATR, HI-6 and various combinations of the two drugs were evaluated against lethal poisoning by soman (GD) and tabun (GA) in guinea pigs. The effect of adjunctive diazepam treattment on the efficacy of atropine and HI-6 against soman was also investigated. Animals of either sex were challenged s.c. with OP and treated i.m. 1 min later with ATR and/or HI-6. When used, diazepam was injected immediately after ATR+HI6. LD50s of each treatment were calculated from probit models based on 24-hour survival against 5 levels of nerve agent and 6 animals per challenge level. A protective index (PI) was calculated by dividing the nerve agent LD50 in the presence of treatment by the LD50 in the absence of treatment. Treatment with HI-6 alone had little effect on the toxicity of either OP Treatment with ATR alone was more effective than HI-6 alone and was significantly more effective against soman than against tabun. When used in combination atropine and HI-6 had a strong synergistic effect against both agents. The dose of atropine used with HI-6 was critical in determining the efficacy of HI-6 against either agent. The slopes of the dose-lethality curves were minimally affected by the dose of ATR or HI-6. Adjunctive treatment with diazepam enhanced the efficacy of HI-6 and atropine against soman. It is concluded that 1) ATR has a large effect on the efficacy of HI-6 against OP poisoning, 2) the dose of ATR must be carefully selected in studies investigating the efficacy of HI-6 against OP poisoning, 3) the effective dose of ATR in the guinea pig is approximately 16 mg/kg, and 4) diazepam is a useful adjunct to atropine and HI-6.     

The Inhibition and Protection of Cholinesterase by Physostigmine and Pyridostigmine Against Soman Poisoning in vivo

It has been shown that some reversible cholinesterase (ChE)inhibitors as physostigmine and pyridostigmine are prophylacticallyeffective in organophosphate poisoning. The inhibition and protectionof ChE against Soman poisoning with the above mentioned drugswas investigated in mice.

1. Physostigmine and pyridostigmine significantly inhibited theChE in whole blood in vivo and their inhibitory potencies withequitoxic doses were approximately equal (1/5 LD₅₀ about 30%;1/2 LD₅₀ about 45% respectively). Physostigmine also significantlyinhibited brain ChE and its potency was slightly weaker thanthat in blood; but pyridostigmine only slightly inhibited brainChE (17%) with large dose (1/2 LD₅₀). The extent of inhibitionwas in parallel with the dosage of the drugs used.
2. Physostigminehad definite protection in the blood and brainChE against Somanpoisoning. The extent of protection was inparallel with thedosage used. The protection of blood ChE bypyridostigmine wasweaker than that by physostigmine. Therewas no protection ofbrain ChE by pyridostigmine.
3. The inhibitory potency of equitoxicdoses of physostigmine andpyridostigmine in the ChE of diaphragmmuscle was equal too(1/2 LD₅₀ about 45%), and the protectiveeffect of physostigminewas still greater than that of pyridostigminein Soman poisoning.
4. The time course of blood ChE inhibitionby physostigmine invivo was of short duration. While 30 minutesafter administrationof physostigmine, the ChE activity graduallyrecovered and itreturned to normal level after 4 hours. Theblood ChE inhibitionby pyridostigmine reached a peak levelafter 2 hours, and theChE activity slowly increased after 4hours, but there was 30%of ChE activity still inhibited after8 hours.
5. Physostigmine and pyridostigmine, the reversibleChE inhibitorswith carbamate structure, have definite ChE protectionagainstSoman poisoning. The prophylactic efficacy was obviouslycorrelatedwith their ChE protective potency. Evaluating physostigmineand pyridostigmine based on their efficacy, toxicity, adverseeffects, duration, availability and stability, we recommendthat pyridostigmine is the drug of choice in the prophylaxisagainst nerve gas poisoning.

     

阿托品与奥美拉唑用于急性胃炎治疗的疗效分析

目的探讨阿托品与奥美拉唑用于急性胃炎治疗的疗效。方法选取我院2016年2月至2018年2月收治的113例急性胃炎患者为研究对象,随机分为观察组57例和对照组56例,对照组给予奥美拉唑联合山莨菪碱治疗,观察组给予奥美拉唑联合阿托品治疗,对比分析两组临床治疗效果。结果观察组治疗总有效率高于对照组(P <0.05);观察组治疗后不良反应发生率低于对照组(P <0.05)。结论在急性胃炎的治疗中应用阿托品联合奥美拉唑治疗可以有效的改善患者的临床症状,降低不良发应的发生概率,安全性更高。     

Comparison of Cholinergic and Neuromuscular Toxicity following Acute Exposure to Sarin and VX in Rat

Comparison of Cholinergic and Neuromuscular Toxicity followingAcute Exposure to Sarin and VX in Rat. GUPTA, R. C, PATTERSON,G. T., AND DETTBARN, W-D. (1991). Fundam. Appl. Toxicol. 16,449–458. Male Sprague-Dawley rats injected with a sublethalsc dosage of 110 µg/ kg of sarin (isopropyl methylphosphonofluoridate),or 12 µg/kg of VX (S-{2-diisopropylaminoethyl) O-ethylmethylphosphonothioate), developed severe toxic signs within5–15 min after sarin and 20–50 min after VX lastingfor 5 to 7 hr. Myonecrotic lesions were seen in soleus and diaphragmmuscles within 1 hr. A maximum number of lesions had developedafter 24 hr, and lesions were also present in extensor digitorumlongus (EDL) at this time. Regeneration of muscle fibers wasslow since lesions were still evident past 7 days of treatment.Within 1 hr following VX, AChE activity was reduced to 8, 12,and 17% of control activity in soleus, diaphragm, and EDL, respectively,whereas with sarin the enzyme activity was reduced to 23, 48,and 82% of control. A still greater inhibition was seen 24 hrafter sarin when AChE activity was reduced to 19, 13, and 43%in these muscles. In skeletal muscles the different molecularforms of AChE, such as 16 S, 12 S, 10 S, and 4 S vary in locationand functional importance with the 16 S form highly concentratedat the neuromuscular junction. All forms in a given muscle wereequally sensitive to the inhibitors. In EDL, sarin was the leasteffective in reducing AChE or its molecular forms. In the brainstructures (cortex, brain stem, striatum, and hippocampus),AChE activity was reduced to 1–6% of control by sarinand VX with the exception that following VX striatal AChE wasreduced to only 41% of control activity. AChE activity in thebrain cortex following either of the agents was maximally affected(1%). A slow but significant recovery of brain AChE was evidentafter 24 hr and more so after Day 7. Butyrylcholinesterase (BuChE)activity was less sensitive to inhibition by both inhibitorscompared to AChE activity and showed a rapid recovery. Basedon the equitoxic doses (toxic signs of similar magnitude), VXwas found to be 10 times more toxic than sarin. The mechanismsof this disparity may be due to differences in rate of uptake,circulation, susceptibility to hydrolysis, and reactivity withnonspecific binding sites.     

A comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX in the rabbit

This study compared the efficacy of HI6 and 2-PAM against nerve agent (soman, tabun, sarin, and VX) -induced lethality in the atropinesterase-free rabbits pretreated with vehicle (controls) or pyridostigmine. Treatment was administered at signs or 2 min after agent challenge and consisted of oxime (100 μmol/kg) + atropine (13 mg/kg) (alone or together with diazepam). Twenty-four-h LD₅₀, values were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival was noted in animals given 10 LD₅₀s of sarin or VX. In pyridostigmine and control rabbits intoxicated with soman and treated with oxime + atropine (alone or together with diazepam), HI6 was 3–5 times more effective than 2-PAM. In contrast, HI6 was less effective than 2-PAM against tabun poisoning. In pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more than 3-fold when compare to tabun-challenged animals treated with atropine + HI6 alone. Both oximes were highly effective against sarin and VX. These findings suggest that HI6 could replace 2-PAM as therapy for nerve agent poisoning, because it is superior to 2-PAM against soman, and when used in pyridostigmine-pretreated animals, it affords excellent protection against all four nerve agents when used in combination with atropine (alone or together with diazepam) therapy.     

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

Humans and rats poisoned with sarin develop chronic neurological disabilities that are not prevented with standardized antidotal therapy. We hypothesized that rats poisoned with the sarin analogue diisopropylfluorophosphate (DFP) and resuscitated with atropine and pralidoxime would have long-term memory deficits that were preventable with naltrexone treatment. Long Evans rats (250–275 g) were randomized to: DFP (N = 8): single subcutaneous (SC) injection of DFP (5 mg/kg). Treatment (N = 9): DFP (5 mg/kg) followed by chronic naltrexone (5 mg/kg/day × 12 weeks). Control (N = 12): single SC injection of isopropyl alcohol, (DFP vehicle) followed by chronic naltrexone (5 mg/kg/day). If toxicity developed after injection, antidotal therapy was initiated with atropine (2 mg/kg) and pralidoxime (25 mg/kg) and repeated as needed. After 12 weeks, rats underwent testing for place learning (acquisition) across 5 days of training using the Morris Water Maze. On day 6 a memory retention test was performed. Statistical analysis was performed using IBM SPSS Statistics. Rats receiving DFP rapidly developed toxicity requiring antidotal rescue. No differences in acquisition were seen between the DFP vs. DFP + naltrexone rats. During memory testing, DFP-poisoned rats spent significantly less time (29.4 ± 2.11 versus 38.5 ± 2.5 s, p < 0.05) and traveled less distance (267 ± 24.6 versus 370 ± 27.5 cm, p < 0.05) in the target quadrant compared to the treatment group. Treatment rats performed as well as control rats (p > 0.05) on the test for memory retention. Poisoning with DFP induced impaired memory retention. Deficits were not prevented by acute rescue with atropine and pralidoxime. Chronic naltrexone treatment led to preserved memory after DFP poisoning.     

溴吡斯的明治疗宫颈癌切除术后尿潴留的临床疗效及安全性评价

目的:分析溴吡斯的明治疗宫颈癌切除术后尿潴留的临床疗效及安全性。方法:选取2012年3月～2017年3月于某院治疗的宫颈癌术后患者68例,按照随机数字表法分为两组,对照组34例口服盐酸坦索罗辛治疗,实验组34例联合口服盐酸坦索罗辛和溴吡斯的明治疗,连续用药1周,比较两组患者的临床疗效及安全性。结果:实验组完全缓解率为61.76%,总有效率为82.35%,均显著高于对照组(P0.05);实验组治疗后膀胱最大容量、最大尿流率、逼尿肌顺应性、逼尿肌压力、残余尿量、疼痛视觉评分(VAS)均低于对照组(P0.05);两组患者总不良反应发生率无显著统计学差异(P0.05)。结论:溴吡斯的明辅助治疗宫颈癌切除术后尿潴留临床疗效显著,改善患者尿动力学水平,安全可靠。     

Effectiveness of Oral Pyridostigmine Pretreatment and Cholinolytic-Oxime Therapy against Soman Intoxication in Nonhuman Primates

Effectiveness of Oral Pyridostigmine Pretreatment and Cholinolytic-OximeTherapy against Soman Intoxication in Nonhuman Primates, VONBREDOW, J. D., ADAMS, N. L., GROFF, W. A., AND VICK, J. A. (1991).Fundam. Appl. Toxicol. 17, 761–770. Nonhuman primateswhich were fed Mestinon (pyridostigmine) syrup-impregnated foodbiscuits (40 mg per animal) exhibited a reproducible inhibitionof whole blood cholinesterase activity of 40 to 50% for a periodof 1 to 6 hr. Pyridostigmine pretreatment was supplemented bytherapy with two doses of an antidotal combination (A,TM,B)consisting of 0.05 mg/kg atropine, 2.24 mg/kg TMB-4, and 0.4mg/kg benactyzine which assured survival in five of six animalsfollowing three separate exposures to 10 LD50 soman. The protectiveperiod of this oral dose of pyridostigmine supported by A,TM,Btherapy was between and 8 hr. Oral pyridostigmine pretreatmentin combination with atropine therapy (three doses of 0.07 or1.00 mg/kg im) also saved monkeys exposed to 10 LD50 soman;however, the period of recovery was prolonged. Oral pyridostigminepretreatment did not alter the lethality of soman in the absenceof A,TM,B or atropine therapy.     

氯磷定持续泵入对急性毒死蜱中毒的疗效分析

目的探讨氯磷定在急性毒死蜱中毒中的应用方法。方法将20例急性毒死蜱中毒患者分A组和B组。A组给予彻底清除毒物,尽早应用阿托品等常规治疗,氯磷定采用传统的反复肌肉注射法;B组氯磷定采用微量泵持续泵入法,其余治疗同A组。比较各组患者的临床疗效和治疗7d内血清胆碱脂酶的活性变化。结果 A组的阿托品总用量、阿托品中毒发生率、反跳率和平均住院天数明显高于B组(P<0.01),而B组的氯磷定总用量显著多于A组(P<0.01)。治疗7d内,B组血清胆碱酯酶活性恢复显著快于A组(P<0.01)。结论急性毒死蜱中毒的救治中,增加氯磷定日总量,采用静脉持续泵入,延长用药时间,经观察疗效明显,用药安全。     

Utility of 2-Pyridine Aldoxime Methyl Chloride (2-PAM) for Acute Organophosphate Poisoning: A Systematic Review and Meta-Analysis

Organophosphates (OP) account for the majority of pesticide-related unintentional or intentional poisonings in lower- and middle-income countries. The therapeutic role of atropine is well-established for patients with acute OP poisoning. The benefit of adding 2-pyridine aldoxime methyl chloride (2-PAM), however, is controversial. We performed a systematic review and meta-analysis of available randomized controlled trials (RCT) to compare 2-PAM plus atropine in comparison to atropine alone for acute OP poisoning. We searched PubMed, EMBASE, and SCOPUS up to March 2017. The Cochrane review handbook was used to assess the risk of bias. Data were abstracted and risk ratios (RR) were calculated for mortality, rate of intubation, duration of intubation, intermediate syndrome, and complications such as hospital-acquired infections, dysrhythmias, and pulmonary edema. We found five studies comprising 586 patients with varying risks of bias. The risk of death (RR = 1.5, 95% CI 0.9–2.5); intubation (RR = 1.3, 95% CI 1.0–1.6); intermediate syndrome (RR = 1.6, 95% CI 1.0–2.6); complications (RR = 1.2, 95% CI 0.8–1.8); and the duration of intubation (mean difference 0.0, 95% CI ? 1.6–1.6) were not significantly different between the atropine plus 2-PAM and atropine alone. Based on our meta-analysis of the available RCTs, 2-PAM was not shown to improve outcomes in patients with acute OP poisoning.     

The oxime pro-2-PAM provides minimal protection against the CNS effects of the nerve agents sarin, cyclosarin, and VX in guinea pigs

This study examined whether pro-2-PAM, a pro-drug dihydropyridine derivative of the oxime 2-pralidoxime (2-PAM) that can penetrate the brain, could prevent or reverse the central toxic effects of three nerve agents; sarin, cyclosarin, and VX. The first experiment tested whether pro-2-PAM could reactivate guinea pig cholinesterase (ChE) in vivo in central and peripheral tissues inhibited by these nerve agents. Pro-2-PAM produced a dose-dependent reactivation of sarin- or VX-inhibited ChE in both peripheral and brain tissues, but with substantially greater reactivation in peripheral tissues compared to brain. Pro-2-PAM produced 9-25% reactivation of cyclosarin-inhibited ChE in blood, heart, and spinal cord, but no reactivation in brain or muscle tissues. In a second experiment, the ability of pro-2-PAM to block or terminate nerve agent-induced electroencephalographic seizure activity was evaluated. Pro-2-PAM was able to block sarin- or VX-induced seizures (16-33%) over a dose range of 24-32 mg/kg, but was ineffective against cyclosarin-induced seizures. Animals that were protected from seizures showed significantly less weight loss and greater behavioral function 24 h after exposure than those animals that were not protected. Additionally, brains were free from neuropathology when pro-2-PAM prevented seizures. In summary, pro-2-PAM provided modest reactivation of sarin- and VX-inhibited ChE in the brain and periphery, which was reflected by a limited ability to block or terminate seizures elicited by these agents. Pro-2-PAM was able to reactivate blood, heart, and spinal cord ChE inhibited by cyclosarin, but was not effective against cyclosarin-induced seizures.     

盐酸戊乙奎醚注射液与阿托品联用治疗急性有机磷中毒临床疗效观察

目的观察盐酸戊乙奎醚注射液（长托宁）与阿托品联用治疗急性有机磷农药中毒（AOPP）的临床疗效。方法对长托宁与阿托品联用肌注治疗AOPP患者31例、长托宁治疗AOPP患者25例、阿托品治疗AOPP患者58例3组临床疗效进行比较。结果与结论长托宁与阿托品联用治疗AOPP是一种比长托宁、阿托品单用抗胆碱能治疗效果更好,不良反应更少的治疗方法,值得在基层医院推广。     

新型选择性长效抗胆碱药物长托宁联合阿托品治疗重度有机磷农药中毒的疗效

目的:探究新型选择性长效抗胆碱药物长托宁联合阿托品治疗重度有机磷农药中毒的疗效。方法:择取2017年1月～2019年1月期间某院收治的40例重度有机磷农药中毒患者,随机分为对照组与观察组各20例。对照组在常规抢救措施基础上给予阿托品治疗,观察组在对照组治疗方案基础上给予长托宁治疗。结果:观察组临床疗效95.00%高于对照组65.00%(P0.05);观察组症状消退时间、胆碱酯酶恢复时间和住院时间少于对照组(P0.05);两组呼吸机使用时间、阿托品化时间差异无统计学意义(P0.05)。结论:针对重度有机磷农药中毒患者实施新型选择性长效抗胆碱药物长托宁联合阿托品治疗效果确切,可有效促进其胆碱酯酶恢复,缩短患者住院时间,对患者的康复具有重要意义。