Naguib Mohamed, Gottumukkala Vijaya, Goldstein Peter A
Department of Anesthesiology and Pain Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
J Pineal Res. 2007 Jan;42(1):12-21. doi: 10.1111/j.1600-079X.2006.00384.x.
The hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a novel hypnotic-anesthetic agent. Sublingually or orally administered melatonin is an effective premedicant in adults and children. Melatonin premedication like midazolam is associated with sedation and preoperative anxiolysis, however, unlike midazolam these effects are not associated with impaired psychomotor skills or the quality of recovery. Melatonin administration also is associated with a tendency toward faster recovery and a lower incidence of postoperative excitement than midazolam. Oral premedication with 0.2 mg/kg melatonin significantly reduces the propofol and thiopental doses required for loss of responses to verbal commands and eyelash stimulation. In rats, melatonin and the more potent melatonin analogs 2-bromomelatonin and phenylmelatonin have been found to have anesthetic properties similar to those of thiopental and propofol, with the added advantage of providing potent antinociceptive effects. The exact mechanism(s) by which structurally diverse intravenous and volatile anesthetics produce general anesthesia is still largely unknown, but positive modulation of gamma-aminobutyric acid type A (GABAA) receptor function has been recognized as an important and common pathway underlying the depressant effects of many of these agents. Accumulating evidence indicates that there is interplay between the melatonergic and GABAergic systems, and it has been demonstrated that melatonin administration produces significant, dose-dependent increases in GABA concentrations in the central nervous system. Additional in vitro data suggest that melatonin alters GABAergic transmission by modulating GABAA receptor function. Of greater importance, data from in vivo studies suggest that the central anesthetic effects of melatonin are mediated, at least in part, via GABAergic system activation, as they can be blocked or reversed by GABAA receptor antagonists. Further work is needed to better understand the general anesthetic properties of melatonin at the molecular, cellular, and systems levels.
褪黑素的催眠、抗伤害感受和抗惊厥特性使其具备新型催眠麻醉剂的特征。经舌下或口服给予的褪黑素对成人和儿童都是有效的术前用药。与咪达唑仑一样，褪黑素术前用药与镇静及术前焦虑减轻相关，但与咪达唑仑不同的是，这些作用与精神运动技能受损或恢复质量无关。与咪达唑仑相比，给予褪黑素还与恢复更快的趋势及术后兴奋发生率较低相关。口服0.2mg/kg褪黑素进行术前用药可显著降低对言语指令和睫毛刺激失去反应所需的丙泊酚和硫喷妥钠剂量。在大鼠中，已发现褪黑素以及更强效的褪黑素类似物2-溴褪黑素和苯基褪黑素具有与硫喷妥钠和丙泊酚相似的麻醉特性，还具有提供强效抗伤害感受作用的额外优势。结构多样的静脉麻醉药和挥发性麻醉药产生全身麻醉的确切机制在很大程度上仍不清楚，但γ-氨基丁酸A型（GABAA）受体功能的正向调节已被认为是许多此类药物抑制作用的重要且常见途径。越来越多的证据表明，褪黑素能系统和GABA能系统之间存在相互作用，并且已证明给予褪黑素会使中枢神经系统中的GABA浓度显著且呈剂量依赖性增加。更多体外数据表明，褪黑素通过调节GABAA受体功能改变GABA能传递。更重要的是，体内研究数据表明，褪黑素的中枢麻醉作用至少部分是通过GABA能系统激活介导的，因为它们可被GABAA受体拮抗剂阻断或逆转。需要进一步开展工作以在分子、细胞和系统水平上更好地理解褪黑素的全身麻醉特性。
