Agmatine as a novel candidate for rapid-onset antidepressant response

Major depressive disorder (MDD) is a disabling and highly prevalent mood disorder as well as a common cause of suicide. Chronic stress, inflammation, and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD. Although conventional antidepressants are widely used in the clinic, they can take weeks to months to produce therapeutic effects. The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD. However, the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use. Therefore, agmatine, an endogenous glutamatergic modulator, has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway, similar to ketamine. However, recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota, which have been shown to play a crucial role in the pathophysiology of MDD, may also participate in the antidepressant-like effects of both ketamine and agmatine. This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies. Considering the anti-inflammatory properties of agmatine, it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state. Moreover, the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.     

Efeitos de tramadol,magnésio e cetamina por via intra‐articular sobre a dor pós‐operatória em meniscectomia artroscópica

Objective

Postoperative pain control is important in terms of early recovery and rehabilitation in arthroscopic meniscectomy. For this purpose, we aimed to compare the effects of intraarticular tramadol, magnesium, and ketamine with combinations of pericapsular bupivacaine on postoperative pain and recovery in arthroscopic meniscectomy.

Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A randomized controlled trial

Study objective

We compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine (SDK) versus morphine in geriatric Emergency Department (ED) patients.

Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine

Introduction. Methoxphenidine is a novel dissociative designer drug of the diarylethylamine class which shares structural features with phencyclidine (PCP), and is not at present subject to restrictive regulations. There is very limited information about the acute toxicity profile of methoxphenidine and the only sources are anonymous internet sites and a 1989 patent of the Searle Company. We report a case of analytically confirmed oral methoxphenidine toxicity. Case details. A 53-year-old man was found on the street in a somnolent and confusional state. Observed signs and symptoms such as tachycardia (112 bpm), hypertension (220/125 mmHg), echolalia, confusion, agitation, opisthotonus, nystagmus and amnesia were consistent with phencyclidine-induced adverse effects. Temperature (99.1°F (37.3°C)) and peripheral oxygen saturation while breathing room air (99%) were normal. Laboratory analysis revealed an increase of creatine kinase (max 865 U/L), alanine aminotransferase (72 U/L) and gamma-glutamyl transpeptidase (123 U/L). Methoxphenidine was identified by a liquid chromatography tandem mass spectrometry toxicological screening method using turbulent flow online extraction in plasma and urine samples collected on admission. The clinical course was favourable and signs and symptoms resolved with symptomatic treatment. Conclusion. Based on this case report and users’ web reports, and compatible with the chemical structure, methoxphenidine produces effects similar to those of the arylcyclohexylamines, as PCP.     

超声引导下腹横平面阻滞联合氯胺酮麻醉与单纯氯胺酮麻醉用于小儿腹股沟疝手术的临床效果

目的探讨超声引导下腹横平面阻滞联合氯胺酮麻醉与单纯氯胺酮麻醉用于小儿腹股沟疝手术的效果及安全性。 方法选择2018年9月至2020年3月川北医学院附属医院收治的80例腹股沟疝患儿作为研究对象,并按照麻醉方案的不同将患者分为观察组与试验组,每组患儿40例。观察组的麻醉方案为单纯氯胺酮静脉麻醉;试验组的麻醉方案为超声引导下腹横平面阻滞联合氯胺酮麻醉。对比2组患儿不同时间点[切皮前（T0）、切皮后10 min（T1）、切皮后15 min（T2）、探查疝囊（T3）]的生命体征、麻醉质量以及进入麻醉恢复室后不同时间点[进入即刻（T4）、进入后20 min（T5）、进入后40 min（T6）]的疼痛情况和镇静情况,及2组患儿的不良反应情况。 结果试验组患儿T1、T2、T3时心率、平均动脉压均显著低于观察组患儿（P<0.05）;2组患儿麻醉诱导时间对比,差异无统计学意义（P>0.05）;试验组苏醒时间均显著低于观察组患儿（P<0.05）;试验组患儿T4、T5、T6时东安大略儿童医院疼痛量表评分、Watcha镇静评分均显著低于观察组患儿（P<0.05）;试验组患儿的不良反应发生率显著低于观察组患儿（P<0.05）。 结论超声引导下腹横平面阻滞联合氯胺酮麻醉对小儿腹股沟疝手术的麻醉效果显著,其麻醉方案不仅能获得更稳定的需流动力学特征,缩短患儿的麻醉苏醒时间,还能改善患儿术后的疼痛及镇静情况。     

氯胺酮鞘内注射对慢性坐骨神经损伤大鼠脊髓 NMDA-2B mRNA表达的影响

目的：探讨氯胺酮连续鞘内注射对慢性坐骨神经损伤大鼠脊髓背角N-甲基-D天冬氨酸亚基（NR2B）mRNA表达的影响。方法：雄性SD大鼠18只，随机分为假手术组、CCI组和氯胺酮组。按Bennett等法制作CCI模型，测von-Frey丝触痛及冷水阈值，采用原位杂交技术检测各组脊髓背角NR2B mRNA表达的变化。结果：CCI组痛阈显著下降，冷水阈显著升高，脊髓背角有大量NR2B mRNA阳性表达（P＜0．01）；氯胺酮组仅出现轻度痛敏症状，NR2B mRNA表达受到明显抑制（P＜0．01）。结论：NR2B mRNA表达上调可能是神经损伤后慢性疼痛的发病机制之一，氯胺酮可抑制其表达从而发挥一定程度的镇痛作用。     

瑞芬太尼、氯胺酮合剂在小儿外科手术中的应用

目的探讨瑞芬太尼联合氯胺酮在小儿外科手术中的应用。方法选择60例ASAⅠ、Ⅱ级手术患儿,术前0.5h肌注阿托品0.02 mg/kg,地西泮0.2~0.4 mg/kg,入手术室后静脉注射氯胺酮2 mg/kg,不行气管内插管,面罩吸氧2 L/min。用微量泵输注"氯-瑞"合剂,开始10 min注速5~15 mL/h,随后根据术中情况调节注药速度。结果患儿术中安静入睡,咽喉反射存在,无躁动、喉痉挛及恶心、呕吐,无明显呼吸抑制现象,分泌物很少,镇痛完善。术毕苏醒时间缩短。结论瑞芬太尼联合氯胺酮用于小儿外科手术是一种很好的联合用药方法。     

小剂量氯胺酮和芬太尼用于妇科术后病人自控镇痛的临床研究

目的 :观察小剂量氯胺酮辅助芬太尼用于妇科手术后静脉病人自控镇痛 (PCIA)的临床效果和安全性。方法 :72例ASAI～II级、在椎管内麻醉下行择期妇科手术病人 ,随机分为三组 ,每组2 4例 ,术后行PCIA。配方I组为芬太尼 0 .75mg 氟哌啶 7.5mg 生理盐水至 15 0ml;II组和III组再分别加入氯胺酮 75mg、15 0mg并用生理盐水稀释至 15 0ml。PCIA设置 :负荷剂量 0 .1ml/kg ,单次给药剂量 0 .0 5ml/kg ,连续给药速度 0 .0 4ml/kg/h ,锁定时间 15分钟。术后 4h、8h、2 4h记录BP、P、RR、芬太尼用量、PCA按压次数 (demand)、疼痛评分 (VAPS)、镇静评分 (VASS)、疲倦评分(VATS)、恶心评分 (VANS)及副作用发生情况。结果 :术后 4h随访时芬太尼用量、PCA按压次数三组间无显著性差异 (P >0 .0 5 )。术后 8h、2 4h随访时III组芬太尼用量、PCA泵按压次数明显少于前二组 (P <0 .0 5 )。结论 :小剂量氯胺酮 (1.1μg /kg/min)与芬太尼联合用于椎管内麻醉妇科手术后PCIA能够减少芬太尼用量 ,并未增加副作用的发生 ,是安全有效的镇痛措施。而 0 .6 5 μg /kg/min的氯胺酮并不产生明显的芬太尼节省效应。     

七氟醚和氯胺酮在小儿扁桃体切除术中麻醉诱导效果比较

【目的】探讨七氟醚、氨胺酮用于小儿扁桃体切除术麻醉诱导效果以及对患者苏醒期躁动期的影响。【方法】本院收治的行扁桃体切除术患儿120例,随机分为七氟醚组（n=60）和氯胺酮组（n=60）,在患儿给予苯巴比妥及阿托品进行全麻之后分别采用七氟醚及氯胺酮麻醉诱导,比较两组患儿麻醉诱导效果以及苏醒期躁动情况。【结果】两组患儿均能够顺利进行手术治疗,并且麻醉效果均良好,无严重事故发生;七氟醚组患儿较氟胺酮组手术时间、拔管时间、苏醒时间均缩短,且两组相比较差异有显著性（P〈0．05）;七氟醚组患儿支气管痉挛发生率、脉搏氧饱和度（SpO2）不稳定发生率均较氯胺酮组显著降低（P〈0．05）;两组患者拔管前平均动脉压（MAP）及心率（HR）差异均无显著性（P〉0．05）,拔管后、拔管后5min七氟醚组患儿HR显著高于氟胺酮组（P〈0．05）,而拔管后七氟醚组MAP显著高于氯胺酮组（P〈0．05）,拔管后5min则差异无显著性（P〉0．05）;七氟醚组患儿躁动发生率为15．00％（20／60）显著低于氯胺酮组63．33％（38／60）,且两组相比较差异具有显著性（P〈0．05）;七氟醚组躁动评分显著低于氯胺酮组（P〈0．05）。【结论】七氟醚较氯胺酮会导致患儿,HR加快、MAP增高,但是能在较短时间内快速恢复;但七氟醚与氯胺酮相比麻醉平稳,患儿术后苏醒快、麻醉时间短、血流动力学平稳、副作用发生率小,苏醒期躁动情况少,更适合于小儿手术。     

序贯法测定异丙酚抑制小剂量氯胺酮兴奋循环作用的半数有效剂量

目的：采用序贯法测定异丙酚(丙泊酚)抑制小剂量氯胺酮兴奋循环作用的半数有效剂量(ED50)。方法择期全身麻醉患者21例,按照序贯法给药原则：丙泊酚剂量按等比数列逐级增加,公比为1.2,初始剂量为0.5 mg/kg。根据静脉注射氯胺酮后血压、脉搏变化情况调整丙泊酚的剂量。记录各时间点的血压、脉搏和SpO2数值及镇痛镇静评分(OAA/S),使用加权均数法计算ED50。结果异丙酚抑制小剂量氯胺酮兴奋循环作用的ED50为0.56 mg/kg,95%可信区间为(0.54,0.62)。结论异丙酚可以有效抑制小剂量氯胺酮的交感神经兴奋作用,两药配伍使用血压、脉搏平稳,呼吸抑制轻微。