A Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Efficacy and Safety of Oral Nalmefene HCI for Alcohol Dependence

A dozen studies have been published showing that opiate antagonists suppress alcohol drinking in animals, and two independent placebo-controlled, double-blind clinical trials of naltrexone found this agent was associated with decreased alcohol craving and consumption in alcohol-dependent patients. Nalmefene is a newer opiate antagonist that has a number of potential advantages over naltrex-one in the treatment of alcoholism, including no dose-dependent association with liver toxicity and more effective binding to central opiate receptors. Consequently, a double-blind pilot study was conducted to gather preliminary data on the safety and efficacy of nalmefene for reducing alcohol consumption in alcohol-dependent subjects. Twenty-one alcohol-dependent subjects meeting admission criteria were randomly assigned to 12 weeks of double-blind treatment with 40 mg nalmefene, 10 mg nalmefene, or placebo, resulting in 7 patients/treatment group. Nalmefene was well tolerated, with no serious adverse drug reactions. The 40 mg group had a significantly lower rate of relapse ( p 0.05), and a greater increase in the number of abstinent days/week ( p 0.09), than the other treatment groups. A significant decrease in the number of drinks/drinking day was noted for both nalmefene groups ( p 0.04), but not for placebo. These results were supported by parallel decreases in ALT. These pilot data provide preliminary support for the hypotheses that nalmefene can be safely given to alcoholics, and that nalmefene may have a role in reducing alcohol consumption and preventing relapse, particularly at the 40 mg level. A full-scale study is underway to confirm these preliminary findings.     

盐酸纳洛酮与盐酸纳美芬用于急性酒精中毒催醒的疗效比较

目的:比较盐酸纳洛酮与盐酸纳美芬用于急性酒精中毒催醒的临床疗效和安全性。方法:124例急性酒精中毒患者随机均分为对照组和观察组。两组患者均给予常规治疗。在此基础上,对照组昏睡者给予盐酸纳洛酮0.4 mg加入5%葡萄糖注射液20 ml中静脉推注,浅昏迷者给予盐酸纳洛酮0.8 mg加入5%葡萄糖注射液20 ml中静脉推注,所有患者再给予盐酸纳洛酮20μg/kg(剂量范围1.2².0 mg)加入5%葡萄糖注射液200 ml中静脉滴注;观察组患者给予盐酸纳美芬0.1 mg加入5%葡萄糖注射液25 ml中静脉推注后,浅昏迷者给予盐酸纳美芬0.2 mg加入5%葡萄糖注射液200 ml中静脉滴注,昏睡者给予盐酸纳美芬0.1mg加入5%葡萄糖注射液200 ml中静脉滴注。两组患者均治疗3 h后评价疗效,观察清醒时间、症状消失时间、用药剂量、平均住院时间、治疗费用及不良反应发生情况。结果:观察组患者总有效率显著高于对照组,清醒时间、症状消失时间、用药剂量、平均住院时间、主治药费、总费用、不良反应发生率均显著低于对照组,两组比较差异均有统计学意义(P<0.05)。结论:盐酸纳美芬用于急性酒精中毒催醒较盐酸纳洛酮疗效更显著,且治疗费用较低,安全性较好。     

纳美芬拮抗先天性心脏病患儿术后呼吸抑制的效果

目的 评价纳美芬拮抗先天性心脏病（先心病）患儿术后阿片类药物所致呼吸抑制的效果.方法 选择行先心病择期手术的患儿60例,采用随机数字表法分为3组（每组20例）：对照组（C组）、Ⅰ组、Ⅱ组.手术结束后,患儿带管送入胸外科重症监护室,待生命体征平稳10 min后：C组（对照组）不给予任何拮抗药;Ⅰ组静脉注射纳美芬0.25 μg/kg;Ⅱ组静脉注射纳美芬0.25μg/kg,观察5 min,再次静脉注射纳美芬0.25μg/kg.记录给药前即刻（T1）、给药后5 min（T2）、给药后30 min（T3）、呼吸恢复时（T4）、拔管时（T5）、拔管后1 h（T6）、拔管后3 h（T7）患儿的平均动脉压（mean arterial pressure,MAP）、心率（heart rate,HR）、脉搏血氧饱和度（pulse oxygen saturation,SpO2）和血气分析结果,记录患儿的呼吸恢复时间、拔管时间及心脏病加强监护病房（cardiac intensive care unit,CICU）监护时间,并观察术后恶心、呕吐、发热、躁动、伤口疼痛等副作用的发生率.结果 C组患儿术后呼吸恢复时间、气管导管拔出时间和CICU监护时间分别为（2.9±1.0）、（3.6±1.4）、（18.5±5.8）h,Ⅰ组分别为（1.8±0.6）、（2.3±0.6）、（8.2±3.1）h,Ⅱ组分别为（1.7±0.5）、（2.1±0.7）、（7.9±2.9）h;与C组比较,Ⅰ组和Ⅱ组的各时间均缩短（P＜0.05）.C组患儿术后恶心、呕吐的发生率为15％,Ⅰ组和Ⅱ组的发生率降低,分别为5％和0（P＜0.05）.结论 纳美芬可安全有效地拮抗先心病手术患儿术后阿片类药物所致呼吸抑制作用,且能减少术后副作用发生率.     

神经节苷脂联合纳美芬对一氧化碳中毒迟发性脑病的治疗作用

目的 观察神经节苷脂联合纳美芬对急性一氧化碳中毒迟发性脑病(DEACMP)患者的治疗作用.方法 2012年1月至2016年3月入住河北医科大学附属哈励逊国际和平急救医学部的128例急性一氧化碳中毒迟发性脑病患者,按随机数字表法分为对照组和治疗组,对照组给予神经节苷脂0.lg肌注、高压氧、防治脑水肿及促进脑细胞代谢等治疗,治疗组在常规治疗基础上加用纳美芬0.3 mg静注,两组分别于治疗前及治疗后2周采取静脉血10 mL检测丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性、一氧化氮(NO)及一氧化氮合酶(NOS)变化,同时观察患者简易精神状态检查量表(MMSE)评分变化,采用t检验比较两组MMSE评分、MDA、NO水平及SOD、GSH-PX、NOS活性的变化,采用X2检验比较治疗2周后两组患者的临床疗效.结果 治疗组总有效率84.4％高于对照组总有效率68.8％,差异有统计学意义(X2=4.354,P=0.037);治疗前两组患者MMSE评分、MDA、NO水平及SOD、GSH-PX、NOS活性比较差异无统计学意义(P＞0.05);治疗后两组患者MDA、NO和NOS水平[对照组:(4.39±1.01) μmol/L、(60.28±9.68) μmol/L、(21.46±5.53) U/mL;治疗组:(3.37±0.83) μmo]/L、(55.29±9.57) μmol/L、(18.71 ±4.40) U/mL]较治疗前[对照组:(5.54±0.96) mol/L、(68.42±12.71)μmol/L、(29.75±6.79) U/mL;治疗组:(5.48 ±1.16) μmol/L、(69.46±16.37) μmol/L、(30.42 ±7.39) U/mL]显著降低(P＜0.05),治疗组低于对照组(P＜0.05);两组患者治疗后MMSE评分及SOD和GSH-PX活性[对照组:(18.30±5.91)、(81.66 ±10.75)U/mL、(60.58 ±9.69) U/L;治疗组:(23.85±7.21)、(96.41±9.64) U/mL、(73.22±9.95)U/L]较治疗前[对照组:(8.93±2.49)、(69.58±8.05) U/mL、(49.35±6.71) U/L;治疗组:(9.14±2.85)、(70.41 ±7.30) U/mL、(48.40±7.89) U/L]均显著提高(P＜0.05),治疗组高于对照组(P＜0.05).结论 神经节苷脂联合纳美芬治疗急性一氧化碳中毒迟发性脑病能有效地降低患者血MDA、NO和NOS的水平、增强SOD和GSH-PX的表达,促进神经功能恢复,临床疗效显著,为指导临床治疗提供重要依据.     

盐酸纳美芬对急性创伤性颅脑损伤患者脑保护作用的临床研究

目的研究急性创伤性颅脑损伤患者应用盐酸纳美芬后血清β-内啡肽(β-EP)、强啡肽(DynA1-13)、神经元特异性烯醇化酶(NSE)的变化,评价盐酸纳美芬对急性创伤性颅脑损伤患者的脑保护作用及不良反应。方法选取急性创伤性颅脑损伤患者40例,并随机分为盐酸纳美芬治疗组和对照组各20例。对照组采用常规治疗,不加用盐酸纳美芬治疗;治疗组在与对照组相同的常规治疗基础上加用盐酸纳美芬治疗。所有患者在治疗前以及治疗后第1、2、3、5、7、10天测定血清β-EP、DynA1-13、NSE的含量,同时记录患者的心率、呼吸频率变化及药物不良反应,对比两组患者3个月后的格拉斯哥预后评分(GOS)。结果治疗组的血清β-EP、DynA1-13、NSE的含量明显低于对照组,其总体变化趋势是下降。对照组的β-EP、DynA1-13的总体变化趋势升高,对照组的NSE总体变化趋势下降。以上三个指标在治疗组与对照组间比较均有显著差异。治疗组的呼吸异常率及心率异常率均低于对照组,差异显著(P0.05)。两组治疗过程中出现的药物不良反应患者例数无显著差异(P0.05)。治疗组与对照组的GOS评分对比有显著差异。结论盐酸纳美芬可降低急性创伤性颅脑损伤后患者血清β-EP、DynA1-13、NSE的含量,能减轻急性创伤性颅脑损伤患者的继发性病理损伤,有一定的脑保护作用,可改善急性创伤性颅脑损伤患者的心率异常率、呼吸异常率及预后。应用盐酸纳美芬后未加重和出现新的不良反应。     

Synergistic effects of cannabinoid inverse agonist AM251 and opioid antagonist nalmefene on food intake in mice

Oral administration of the opioid antagonist nalmefene alone (up to 20 mg/kg) failed to show a significant effect on acute food intake in mice. However, combined oral dosing of nalmefene and subthreshold doses of AM251, a cannabinoid CB1 receptor inverse agonist, led to a significant reduction in food intake in both lean and diet-induced obese (DIO) mice. Furthermore, the anorectic effect of a high dose of AM251 was further enhanced when co-administered with nalmefene. The results support a synergistic interaction between opioid and cannabinoid systems in regulating feeding behavior.     

纳美芬不同给药时机对全麻下腹腔镜全子宫切除术后苏醒期躁动的影响

目的 观察纳美芬不同给药时机对全麻下腹腔镜全子宫切除术后苏醒期间躁动的影响.方法 选择90例按美国麻醉医师协会（American Society of Anesthesiologists ASA）1～2级需要在全麻下行腹腔镜全子宫切除术的患者,随机分为三组,每组30例,分别在麻醉停药前5min（A组）,麻醉停药时（B组）和麻醉停药后5min（C组）静脉注入纳美芬0.25μg/kg.三组麻醉诱导及麻醉维持方法均相同.分别纪录麻醉维持时间、呼吸恢复时间、拔气管导管时间、拔管10min后的呼吸次数、拔管时镇静-躁动（RASS）评分及拔管后10min视觉模拟评分（VAS）.结果 三组患者麻醉维持时间差异均无显著性（P＞0.05）.A组与B组之间呼吸恢复时间、拔管时间和拔管后10min呼吸次数（次/分）差异均无显著性（P＞0.05）,A组和B组与C组之间呼吸恢复时间、拔管时间和拔管后10min呼吸次数（次/分）差异均有显著性（P＜0.05）,A组和B组比C组促进呼吸恢复的效果更明显;B组和C组与A组之间镇静—躁动评分和疼痛程度评分均差异有显著性（P＜0.05）,B组和C组比A组预防躁动和减轻术后10min疼痛效果更好.结论 全麻麻醉停药时静脉注入小剂量纳美芬,能够有效减少腹腔镜全子宫切除术后全麻苏醒期躁动的发生,并能促进呼吸的恢复.     

Nalmefene decreases meal size, food and water intake and weight gain in Zucker rats

Opioids are proposed to play a role in the control of food intake since administration of opioids increase food intake while administration of opioid antagonists decrease food intake. In these experiments responses to a new opioid antagonist, nalmefene, were measured in Zucker obese and lean rats. In obese male rats 1 mg/kg nalmefene decreased the size of the first meal after a 10-hr fast and decreased 14-hr food intake, indicating nalmefene is relatively long-acting. Administration of 1 mg/kg nalmefene daily for 7 days decreased average meal size and daily food intake and increased meal frequency; feeding responses on day 7 were similar to those on day 1, suggesting a lack of development of tolerance. Food and water intake and weight gain during a 3-week treatment period were decreased more in lean rats by low doses of nalmefene (up to 0.25 mg/kg) and more in obese rats by higher doses of nalmefene (0.50 mg/kg). These responses to a new opioid antagonist further support a possible role for opioids in the control of food intake.     

盐酸纳美芬治疗重症手足口病的疗效分析

目的观察盐酸纳美芬治疗重症手足口病(HFMD)的临床疗效。方法采取随机、对照的研究方法将2009年5月至8月开封市儿童医院重症监护病房(PICU)173例重症HFMD患儿随机分为对照组、纳美芬组。比较两组患儿在PICU平均住院时间、机械通气时间、肺水肿、肺出血发生率等。结果对照组患儿在PICU平均住院时间、呼吸机应用率、休克及肺水肿/肺出血发生率均明显高于纳美芬组(P<0.05)。结论盐酸纳美芬治疗重症HFMD可以改善患儿的临床症状,提高其治愈率。     

纳美芬治疗急性酒精中毒疗效分析

目的分析纳美芬在治疗急性酒精中毒患者中的疗效及安全性。方法将2009年4月至2010年4月收治的120例急性酒精中毒患者随机分成对照组和治疗组,其身体状况、饮酒情况等差异均无统计学意义。两组在常规治疗的基础上,对照组兴奋期和共济失调期、昏迷期分别给予纳洛酮0.8 mg、1.2 mg加入0.9%氯化钠液250 ml静脉滴注,严重者需重复用药;治疗组兴奋期和共济失调期、昏迷期分别给予纳美芬0.1 mg、0.2 mg加入0.9%氯化钠液250 ml中静脉滴注。观察患者意识恢复、语言能力、共济失调及不良反应情况。结果在2 h和5 h内,两组的治愈率和总有效率相比,差异有统计学意义。结论纳美芬在治疗急性酒精中毒中疗效显著,作用时间长,不良反应少,安全可靠。