丙泊酚对异氟烷镇痛、催眠效应的影响

目的 观察丙泊酚对异氟烷镇痛、催眠效应的影响.方法 试验小鼠120只(雌雄比2:1)随机分为热板法试验组(n=40,雌性)、甩尾法试验组(n=40,雌雄各半)和催眠试验法组(n=40,雌雄各半),各组再按分层随机设计分为NS组(生理盐水组)、Pp组(丙泊酚组)、Iso组(异氟烷组)和Pp+Iso组(丙泊酚与异氟烷合用组...     

羟丁酸钠与恩氟烷合用对小鼠镇痛催眠作用的影响

目的 观察羟丁酸钠对恩氟烷镇痛、催眠作用的影响.方法 120只受试小鼠随机分为热板法试验组(n=40,均为雌性)、扭体法试验组(n=40,雌雄各半)及催眠试验组(n=40,雌雄各半).各组再按分层随机区组设计分为生理盐水组(NS组)、羟丁酸钠组(SO组)、恩氟烷组(En组)和羟丁酸钠与恩氟烷合用组(SO+En组),观察...     

羟丁酸钠对瑞芬太尼镇痛作用的影响

目的观察羟丁酸钠对瑞芬太尼镇痛效果的影响。方法试验小鼠48只,随机分为热板法试验组（n=24,均为雌性）和扭体法试验组（n=24,雌雄各半）,各组再按分层随机区组设计各分为甲组（羟丁酸钠和生理盐水合用组）、乙组（瑞芬太尼和生理盐水合用组）和丙组（羟丁酸钠和瑞芬太尼合用组）,分别以热板法和扭体法观察羟丁酸钠对瑞芬太尼镇痛小鼠热板法痛阈（HPPT）和扭体次数的影响。结果热板法试验提示,与丙组相比,甲组和乙组在5、10和20min时HPPT均降低,5和20min时降低显著（P〈0．01）。扭体试验结果显示,与丙组相比,甲组和乙组小鼠扭体次数增加,差异显著（P〈0．01）。结论羟丁酸钠可增强瑞芬太尼的镇痛效应。     

神经元烟碱受体与异氟烷、七氟烷催眠和镇痛作用的关系

目的探讨神经元烟碱受体(neuronal nicotinic acetyl-choline receptors,nnAChRs)与异氟烷、七氟烷催眠和镇痛作用的关系。方法建立小鼠催眠、镇痛模型后,在催醒、热板和扭体实验中分别观察侧脑室(intracerebroventricular,icv)或鞘内(intrathecal,it)注射不同剂量烟碱(nicotine,N)对小鼠睡眠时间(sleeping time,ST)、热板法痛阈(pain threshold in hot-plate test,HPPT)和扭体次数的影响。结果催醒实验中,烟碱10、20、40μgicv能够剂量依赖性地缩短异氟烷、七氟烷催眠小鼠的ST(P<0·05,P<0·01);热板实验中,烟碱5、10、15μgit对清醒小鼠HPPT没有影响(P>0·05),但能够剂量依赖性地减少异氟烷、七氟烷镇痛小鼠的HPPT(P<0·05,P<0·01);扭体实验中,皮下注射镇痛剂量的异氟烷、七氟烷后均能引起小鼠的扭体次数减少(P<0·01),但烟碱5、10、15μgit对异氟烷、七氟烷镇痛小鼠的扭体次数的影响差异均无显著性(P>0·05)。结论nnAChRs是异氟烷、七氟烷催眠作用的重要靶位;也是异氟烷、七氟烷抗热刺激伤害的重要靶位,但与其抗化学内脏痛作用关系不大。     

γ-羟基丁酸受体与恩氟烷、异氟烷镇痛、催眠作用的关系

目的探讨γ-羟基丁酸(gamma-hydroxybutyric acid,GHBA)受体与吸入麻醉药异氟烷和恩氟烷催眠、镇痛作用的关系。方法建立小鼠腹腔和皮下注射吸入麻醉药催眠、镇痛模型。在催醒、热板和扭体实验中分别观察侧脑室(intracerebroventricular,icv)或鞘内(intrathecal,it)注射不同剂量GHBA受体拮抗剂NCS-382对小鼠睡眠时间(sleepingtime,ST)、热板疼痛指数(pain index in hot-plate test,HPPI)和扭体次数(writhing times)的影响。结果催醒实验中,NCS-3821、5、25μg icv均可使异氟烷和恩氟烷催眠小鼠的ST缩短(P<0.01);热板实验中,NCS-3821、5、25μg it对清醒和镇痛小鼠的HPPI没有影响(P>0.05);扭体实验中,皮下注射异氟烷和恩氟烷后引起小鼠的扭体次数减少(P<0.01),但NCS-3821、5、25μg it对清醒小鼠及镇痛小鼠的扭体次数均无明显影响(P>0.05)。结论γ-羟基丁酸受体是吸入麻醉药异氟烷和恩氟烷催眠作用的靶位之一,但与其抗热刺激伤害和抗化学内脏痛作用关系不大。     

瞬时感受器电位香草酸受体1对异氟烷镇痛和催眠作用的影响

目的探讨瞬时感受器电位香草酸受体1(TRPV1)对异氟烷镇痛及催眠作用的影响。方法在热板法和扭体法镇痛实验中,80只小鼠随机均分为生理盐水(NS组)和异氟烷(异氟烷组,腹腔注射异氟烷1.0 ml/kg)两组;随后各组再均分为4个亚组,分别注射溶媒、辣椒素(125、250、500ng/kg)。记录热板法热板痛阈(HPPT)和扭体法扭体次数。催眠实验中,异氟烷组小鼠腹腔注射异氟烷1.0 ml/kg后,侧脑室注射溶媒、辣椒素(125、250、500 ng/kg),记录给药后小鼠的睡眠时间(ST)。结果与异氟烷+溶媒亚组相比,其余3个异氟烷+辣椒素亚组HPPT降低(P<0.05)、扭体次数增加(P<0.01),但ST无明显变化(P>0.05)。结论 TRPV1可能是异氟烷抗热刺激痛和内脏化学刺激痛的靶位之一,但与异氟烷的催眠作用关系不大。     

异氟烷麻醉对脊柱骨折大鼠神经功能、镇痛及脊髓c-FOS蛋白的影响

目的 探讨异氟烷麻醉对脊柱骨折大鼠神经功能、镇痛及脊髓c-FOS蛋白的影响。方法 随机将40只大鼠分为4组,健康组(Health group, HEA组)、模型组(Model group, MOD组)、低剂量异氟烷组(Low-dose isoflurane group, LDI组)、高剂量异氟烷组(High-dose isoflurane group, HDI组)。酶联免疫法检测大鼠血清中炎性因子水平,参照Longa及Bederson对大鼠神经功能进行评分,Western blot法及免疫组化法检测大鼠脊髓背角组织中c-FOS及SP蛋白表达。结果 与HEA组比较,MOD组、LDI组和HDI组大鼠神经功能评分指数、各时间段足伸姿推力(Elevated posture thrust, EPT)、TNF-α及IL-6水平、c-FOS及SP蛋白表达及阳性表达率升高,各时间段后肢撤足阈值(Paw withdrawal threshold, PWT)均降低(P<0.05);与MOD组相比,LDI组和HDI组大鼠神经功能评分指数降低,大鼠神经功能评分指数、各时间段EPT、TNF-α、IL-6水...     

咪达唑仑对异氟烷小鼠的镇痛、催眠作用的影响

<正>异氟烷(Isoflurane,Iso)是临床常用吸入麻醉药。有研究发现[1],GHB受体、神经元烟碱受体与吸入麻醉药的催眠作用有关,而NMDA、GlyR及AMPA与其镇痛作用有关,但是GABA受体与吸入麻醉药的镇痛作用的关系还不明确[2]。咪达唑仑(Midazolam,Mid)是一种含咪唑环的苯二氮     

口服异氟烷、七氟烷对小鼠的麻醉作用观察

目的:观察口服异氟烷(Iso)、七氟烷(Sev)对小鼠的镇痛及催眠等麻醉作用。方法:按分层随机设计,将180只小鼠分为18组(n=10),分别用于热板实验、扭体实验(各60只):对照组(生理盐水(NS)组),Iso1、Iso2、Iso3组(1、2、3mL·kg-1),Sev1、Sev2组(5、10mL·kg-1)。催眠实验(60只):对照组(NS组),Iso1、Iso2、Iso3组(6、8、10mL·kg-1),Sev1、Sev2组(20、40mL·kg-1)。小鼠Iso、Sev灌胃后用热板和扭体实验观察小鼠热板痛阈值(HPPT)和扭体次数的变化情况,以评估镇痛作用;用催眠实验的睡眠时间变化情况评估催眠作用。结果:与对照组比较,Iso(1～3mL·kg-1)、Sev(5、10mL·kg-1)灌胃能增加HPPT值,减少扭体次数(P<0.05,P<0.01);Iso(6～10mL·kg-1)、Sev(20、40mL·kg-1)灌胃后能延长睡眠时间(P<0.01)。结论:在本实验条件下,小鼠Iso、Sev灌胃可产生有效的催眠和镇痛等麻醉作用。     

鞘内注射p-MPPF对异氟烷镇痛作用的影响

目的探讨异氟烷(isoflurane,Iso)镇痛作用与小鼠脊髓5-HT1A受体的关系。方法昆明种小鼠腹腔注射Iso建立镇痛模型。分别以甩尾法、热板法、醋酸扭体法(15min内)评估小鼠鞘内注射5-HT1A受体拮抗剂p-MPPF(6μg和3μg)对Iso镇痛作用的影响。结果单独鞘内注射p-MPPF对小鼠甩尾潜伏期、热板痛阈、扭体次数无影响(P>0.05)。与Iso镇痛组(Iso组)相比,合用药组(Iso+M6组,Iso+M3组)甩尾潜伏期与热板痛阈均缩短(P<0.01或P<0.05);Iso+M6组扭体次数较Iso组增多(P<0.05),Iso+M3组无变化(P>0.05)。结论 Iso体表镇痛作用与激动小鼠脊髓5-HT1A受体密切相关。     

γ-羟基丁酸受体在羟丁酸钠保护大鼠海马缺氧复氧损伤中的作用

目的探讨γ-氨基丁酸(GABA)受体与γ-羟基丁酸(GHB)受体在羟丁酸钠(SO)对脑缺血的保护中何者更重要,为临床治疗脑缺血再灌注损伤寻找新的药物靶标。方法采用大鼠海马脑片缺氧复氧(H-R)损伤模型。设正常对照组、H-R模型组、SO1,10和100μmol·L-1组;NCS-382(GHB受体拮抗剂)100μmol·L-1组、荷包牡丹碱(Bic,GABAA受体拮抗剂)100μmol·L-1+saclofen(Sac,GABAB受体拮抗剂)100μmol·L-1(Bic+Sac)组、SO100μmol·L-1+NCS-382100μmol·L-1(SO+NCS-382)组、SO100μmol·L-1+Bic100μmol·L-1+Sac100μmo·lL-1(SO+Bic+Sac)组和SO100μmol·L-1+NCS-382100μmo·lL-1+Bic100μmol·L-1+Sac100μmol·L-1(SO+NCS-382+Bic+Sac)组。用比色法测定乳酸脱氢酶(LDH)释放率及TTC染色法检测脑组织损伤。结果模型组LDH释放率为(41.5±8.1)%,明显高于对照组(n=6,P<0.01);TTC染色的A490nm值为0.030±0.008,显著低于对照组(n=6,P<0.01)。SO1,10和100μmo·lL-1组的LDH释放率较模型组显著降低(n=6,P<0.05,P<0.01,P<0.01);TTC染色的A490nm值则明显升高(n=6,P<0.05,P<0.01,P<0.01)。单用GHB受体阻断剂NCS-382,或联合使用GABAA与GABAB受体阻断剂Bic+Sac,LDH释放率和TTC染色的A490nm值均接近模型组(n=6,P>0.05)。SO+NCS-382组LDH释放率较SO100μmol·L-1组明显升高(n=6,P<0.01);SO+NCS-382组和SO+Bic+Sac组TTC染色的A490nm值较SO100μmol·L-1组显著降低(n=6,P<0.01,P<0.05);而SO+NCS-382+Bic+Sac组LDH释放率和TTC染色的A490nm值都与SO100μmol·L-1组有明显差异(n=6,P<0.01),且较SO+Bic+Sac组更明显(n=6,P<0.01),但与SO+NCS-382比较没有明显差异。结论阻断GHB受体比阻断GABA受体对SO对大鼠海马脑片H-R损伤的保护作用影响更大。     

羟丁酸钠对沙土鼠脑缺血损伤的保护作用

目的　探讨羟丁酸钠 (SO)对沙土鼠全脑缺血有无保护作用 ,为其新的临床应用提供理论依据。方法　采用双侧颈总动脉结扎法制作全脑缺血 ( 10min)再灌注损伤模型 ,观察SO( 5 0 ,10 0 ,2 0 0mg·kg- 1,ip ,每日 1次 ,连续 7d)对脑缺血后神经功能和海马组织损伤的影响。缺血后d 3 ,d 7用开场行为测试法检测自发活动 ,d 4,d 5 ,d 6用T迷宫测试学习记忆能力 ,d 7进行海马CA1区神经元病理学检查。结果　SO能降低脑缺血沙土鼠的自发活动 ,提高其学习记忆能力 ,并且显著减轻海马CA1区锥体神经元的损伤 ,其作用呈剂量依赖性。结论　SO对脑缺血损伤有一定的保护作用。     

A review of sodium oxybate and baclofen in the treatment of sleep disorders

Studies examining GABA(B) receptor agonists have reported effects on sleep including decreased sleep onset latency (SOL), increased sleep consolidation and increases in slow wave sleep (SWS). γ-hydroxybutyrate (GHB) is proposed to act as a GABA(B) receptor agonist; however, the mechanism of action of GHB is controversial. In addition, the GABA(B) receptor agonist, baclofen, has also been proposed to exert similar effects on sleep. The aim of this paper is to provide a review of the human clinical studies of sodium oxybate and baclofen regarding sleep and the treatment of sleep disorders including narcolepsy and insomnia, as well as other disorders involving disrupted sleep such as fibromyalgia.     

An evaluation of sodium oxybate as a treatment option for narcolepsy

Introduction: Narcolepsy is a lifelong central nervous system (CNS) disorder characterized by excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep, hypnagogic hallucinations, and sleep paralysis. Treatment is symptomatic and challenging. Current therapies with wake promoting agents, stimulants, and antidepressants improve symptoms but residual sleepiness or cataplexy may persist. Drug tolerance may develop. Adverse drug effects limit therapy. In the United States, sodium oxybate has been approved to treat daytime sleepiness and cataplexy in adults with narcolepsy since 2002. In 2018, it was approved for children ages 7–17 years with cataplexy with narcolepsy.

Areas covered: This drug review includes an overview of narcolepsy, current pharmacotherapy, drug chemistry, pharmacodynamics, pharmacokinetics, and metabolism of sodium oxybate. Published results from 11 randomized control trials are reviewed. Databases searched included PubMed, Google Scholar, Lexi-Comp, Scopus, Science, and Ovid.

Expert opinion: Sodium oxybate is an effective therapy for excessive daytime sleepiness and cataplexy in adults and children ages 7–17 years. It is also an effective therapy for disrupted nocturnal sleep. Sodium oxybate improves narcolepsy symptoms and enhances quality of life in narcolepsy patients.     

帕瑞昔布钠对腰椎内固定术后静脉镇痛效果的影响

目的观察帕瑞昔布钠对骨科腰椎内固定手术后静脉镇痛效果的影响。方法选择择期在全麻下行腰椎内固定手术患者60例,随机分为2组,每组30例。两组均在手术结束前30 min分别给予帕瑞昔布钠40 mg(A组,生理盐水稀释为2 mL)或生理盐水2 mL(B组)。术毕即开始使用舒芬太尼进行静脉自控镇痛(PCA)。采用VAS评分记录两组患者苏醒时及术后2、4、8、24、48 h的镇痛效果,记录患者24 h、48 h内PCA有效按压次数及舒芬太尼使用量,同时观察术后各时间点患者Ramsay镇静评分及不良反应。结果与B组比较,A组患者术后各时间点VAS评分显著降低(P<0.05),PCA有效按压次数及术后24 h舒芬太尼使用总量显著减少(P<0.05);两组患者Ramsay镇静评分比较差异无统计学意义(P>0.05),镇痛期间各种不良反应发生率比较差异无统计学意义(P>0.05)。结论静脉注射帕瑞昔布钠40 mg用于腰椎内固定手术术后镇痛可以增强舒芬太尼PCA镇痛效果。     

gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness

gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations.Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO(2) and H(2)O through the tricarboxylic acid cycle (Krebs cycle). Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.     

The influence of gender and food on the pharmacokinetics of sodium oxybate oral solution in healthy subjects

Sodium oxybate (Xyrem; gamma-hydroxybutyrate) oral solution was recently approved in the United States for the treatment of cataplexy in patients with narcolepsy. Two single-center, randomized, open-label studies in healthy volunteers receiving single oral 4.5-g doses of sodium oxybate evaluated effects of (1) gender on oxybate pharmacokinetics and (2) food on its oral bioavailability. In the latter study, one dose was administered after an overnight fast, another after a high-fat meal; 1 week separated treatments. Sodium oxybate pharmacokinetics was not significantly different between sexes. However, food significantly altered the bioavailability of oxybate by decreasing mean peak plasma concentration, increasing median time-to-peak concentration, and decreasing the area under the plasma concentration-time curve. Food did not affect elimination and urinary excretion of unchanged drug. No dose adjustment of sodium oxybate based on sex is indicated. Although significant food effects were observed, these are minimized in patients by the nocturnal dosing of sodium oxybate hours after the evening meal at a consistent time interval following food ingestion.