法医学杂志 ›› 2025, Vol. 41 ›› Issue (2): 127-135.DOI: 10.12116/j.issn.1004-5619.2024.341002
所属专题: 中毒的法医学鉴定专题
左雨蒙1,2,3(
), 韩卫1,2,3(
), 张建波1,2,3, 李涛1,2,3(
)
收稿日期:2024-10-19
发布日期:2025-08-11
出版日期:2025-04-25
通讯作者:
韩卫,李涛
作者简介:左雨蒙(1999—),女,硕士,主要从事法医学研究;E-mail:Zymzxw@stu.xjtu.edu.cn
基金资助:
Yu-meng ZUO1,2,3(
), Wei HAN1,2,3(
), Jian-bo ZHANG1,2,3, Tao LI1,2,3(
)
Received:2024-10-19
Online:2025-08-11
Published:2025-04-25
Contact:
Wei HAN, Tao LI
摘要:
氯胺酮是一种解离性麻醉剂,临床上作为手术麻醉剂或麻醉诱导剂,具有一定精神依赖性,滥用可导致神经损伤、不良情绪反应等毒副作用。氯胺酮发挥药理作用的主要机制为阻滞N-甲基-D-天冬氨酸受体,此外,也通过α-氨基-3-羟基-5-甲基-4-异噁唑丙酸受体、阿片受体、γ-氨基丁酸受体、单胺能受体、胆碱能受体、超极化激活的环核苷酸门控通道、电压门控钠通道和L型电压依赖性钙通道等途径发挥作用。本文对氯胺酮发挥药理学作用的分子生物学机制及毒性效应进行总结,以期为鉴别氯胺酮毒性效应的症状表型和滥用氯胺酮的鉴定等法医学应用提供依据。
中图分类号:
左雨蒙, 韩卫, 张建波, 李涛. 氯胺酮的分子生物学机制及毒性效应[J]. 法医学杂志, 2025, 41(2): 127-135.
Yu-meng ZUO, Wei HAN, Jian-bo ZHANG, Tao LI. Molecular Mechanisms and Toxic Effects of Ketamine[J]. Journal of Forensic Medicine, 2025, 41(2): 127-135.
| [1] | JOHNSTON J N, HENTER I D, ZARATE C A. The antidepressant actions of ketamine and its enantiomers[J]. Pharmacol Ther,2023,246:108431. doi:10.1016/j.pharmthera.2023.108431 . |
| [2] | REICH D L, SILVAY G. Ketamine: An update on the first twenty-five years of clinical experience[J]. Can J Anaesth,1989,36(2):186-197. doi:10.1007/bf03011442 . |
| [3] | HIROTA K, LAMBERT D G. Ketamine; History and role in anesthetic pharmacology[J]. Neuropharmacology,2022,216:109171. doi:10.1016/j.neuropharm.2022.109171 . |
| [4] | SASSANO-HIGGINS S, BARON D, JUAREZ G, et al. A review of ketamine abuse and diversion[J]. Depress Anxiety,2016,33(8):718-727. doi:10.1002/da.22536 . |
| [5] | 杨航,陆方舟,杨春,等. 氯胺酮拟精神症状及奖励机制的研究进展[J].中国临床药理学与治疗学,2022, 27(12):1347-1353. doi:10.12092/j.issn.1009-2501.2022.12.004 . |
| YANG H, LU F Z, YANG C, et al. Research progress of ketamine psychomimetic symptoms and reward mechanism[J]. Zhongguo Linchuang Yaolixue Yu Zhiliaoxue,2022,27(12):1347-1353. | |
| [6] | WEINER A L, VIEIRA L, MCKAY C A, et al. Ketamine abusers presenting to the emergency department: A case series[J]. J Emerg Med,2000,18(4):447-451. doi:10.1016/s0736-4679(00)00162-1 . |
| [7] | 杨菊,李小静,张志湘,等. 成年小鼠氯胺酮慢性中毒后脑细胞凋亡[J].法医学杂志,2013,29(5):325-329. doi:10.3969/j.issn.1004-5619.2013.05.002 . |
| YANG J, LI X J, ZHANG Z X, et al. Apoptosis in adult mouse brain after chronic poisoning of ketamine[J]. Fayixue Zazhi,2013,29(5):325-329. | |
| [8] | MA S, CHEN M, JIANG Y, et al. Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb[J]. Nature,2023,622(7984):802-809. doi:10.1038/s41586-023-06624-1 . |
| [9] | YEUNG L Y, WAI M S M, FAN M, et al. Hyperphosphorylated tau in the brains of mice and monkeys with long-term administration of ketamine[J]. Toxicol Lett,2010,193(2):189-193. doi:10.1016/j.toxlet.2010.01.008 . |
| [10] | WU Q L, GAO Y, LI J T, et al. The role of AMPARs composition and trafficking in synaptic plasticity and diseases[J]. Cell Mol Neurobiol,2022,42(8):2489-2504. doi:10.1007/s10571-021-01141-z . |
| [11] | DIERING G H, HUGANIR R L. The AMPA receptor code of synaptic plasticity[J]. Neuron,2018,100(2):314-329. doi:10.1016/j.neuron.2018.10.018 . |
| [12] | SATHLER M F, KHATRI L, ROBERTS J P, et al. Phosphorylation of the AMPA receptor subunit GluA1 regulates clathrin-mediated receptor internalization[J]. J Cell Sci,2021,134(17):jcs257972. doi:10 . |
| 1242/jcs.257972. | |
| [13] | NOSYREVA E, SZABLA K, AUTRY A E, et al. Acute suppression of spontaneous neurotransmission drives synaptic potentiation[J]. J Neurosci,2013,33(16):6990-7002. doi:10.1523/jneurosci.4998-12.2013 . |
| [14] | LI N, LEE B, LIU R J, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists[J]. Science,2010,329(5994):959-964. doi:10.1126/science.1190287 . |
| [15] | ZANOS P, MOADDEL R, MORRIS P J, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites[J]. Nature,2016,533(7604):481-486. doi:10.1038/nature17998 . |
| [16] | KATARI V, DALAL K K, KONDAPALLI N, et al. Opioid receptors in cardiovascular function[J]. Br J Pharmacol,2025,182(16):3710-3725. doi:10.1111/bph.70097 . |
| [17] | TRESCOT A M, DATTA S, LEE M, et al. Opioid pharmacology[J]. Pain Physician,2008,11(S2):133-153. |
| [18] | GRAY A C, COUPAR I M, WHITE P J. Comparison of opioid receptor distributions in the rat central nervous system[J]. Life Sci,2006,79(7):674-685. doi:10.1016/j.lfs.2006.02.021 . |
| [19] | MERCER LINDSAY N, CHEN C, GILAM G, et al. Brain circuits for pain and its treatment[J]. Sci Transl Med,2021,13(619):eabj7360. doi:10.1126/scitranslmed.abj7360 . |
| [20] | BAPTISTA-HON D T, SMITH M, SINGLETON S, et al. Activation of μ-opioid receptors by MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) and its fluorinated derivatives[J]. Br J Pharmacol,2020,177(15):3436-3448. doi:10.1111/bph.15064 . |
| [21] | HUSTVEIT O, MAURSET A, OYE I. Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors[J]. Pharmacol Toxicol,1995,77(6):355-359. doi:10.1111/j. 1600-0773.1995.tb01041.x . |
| [22] | GAGE P W, ROBERTSON B. Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus[J]. Br J Pharmacol,1985,85(3):675-681. doi:10.1111/j.1476-5381.1985.tb10563.x . |
| [23] | FLOOD P, KRASOWSKI M D. Intravenous anesthetics differentially modulate ligand-gated ion channels[J]. Anesthesiology,2000,92(5):1418-1425. doi:10.1097/00000542-200005000-00033 . |
| [24] | KRYSTAL J H, KAYE A P, JEFFERSON S, et al. Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments[J]. Proc Natl Acad Sci USA,2023,120(49):e2305772120. doi:10.1073/pnas.2305772120 . |
| [25] | WOHLEB E S, GERHARD D, THOMAS A, et al. Molecular and cellular mechanisms of rapid-acting antidepressants ketamine and scopolamine[J]. Curr Neuropharmacol,2017,15(1):11-20. doi:10.2174/1570159x14666160309114549 . |
| [26] | PETERS K Z, CHEER J F, TONINI R. Modulating the neuromodulators: Dopamine, serotonin, and the endocannabinoid system[J]. Trends Neurosci,2021,44(6):464-477. doi:10.1016/j.tins.2021.02.001 . |
| [27] | 钟佳君,刘妍,刘兴阳,等. 人参皂苷调节配体门控离子通道研究进展[J].中国药理学与毒理学杂志,2024,38(12):932-944. doi:10.3867/j.issn.1000-3002.2024.12.005 . |
| ZHONG J J, LIU Y, LIU X Y, et al. Research progress in roles of ginsenosides in regulating ligand-gated ion channels[J]. Zhongguo Yaolixue Yu Dulixue Zazhi,2024,38(12):932-944. | |
| [28] | KOKKINOU M, ASHOK A H, HOWES O D. The effects of ketamine on dopaminergic function: Meta-analysis and review of the implications for neuropsychiatric disorders[J]. Mol Psychiatry,2018,23(1):59-69. doi:10.1038/mp.2017.190 . |
| [29] | RÉUS G Z, MATIAS B I, MACIEL A L, et al. Mechanism of synergistic action on behavior, oxidative stress and inflammation following co-treatment with ketamine and different antidepressant classes[J]. Pharmacol Rep,2017,69(5):1094-1102. doi:10.1016/ |
| j.pharep.2017.04.021. | |
| [30] | SEEMAN P, KO F, TALLERICO T. Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics[J]. Mol Psychiatry,2005,10(9):877-883. doi:10.1038/sj.mp.4001682 . |
| [31] | KAPUR S, SEEMAN P. NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors — Implications for models of schizophrenia[J]. Mol Psychiatry,2002,7(8):837-844. doi:10.1038/sj.mp.4001093 . |
| [32] | AGO Y, TANABE W, HIGUCHI M, et al. (R)-keta-mine induces a greater increase in prefrontal 5-HT release than (S)-ketamine and ketamine metabolites via an AMPA receptor-independent mechanism[J]. Int J Neuropsychopharmacol,2019,22(10):665-674. doi:10.1093/ijnp/pyz041 . |
| [33] | CRISP T, PERROTTI J M, SMITH D L, et al. The local monoaminergic dependency of spinal keta-mine[J]. Eur J Pharmacol,1991,194(2/3):167-172. doi:10.1016/0014-2999(91)90101-u . |
| [34] | 章文欣,周冬雨,韩奕,等. NMDA受体与α2肾上腺素受体参与神经精神疾病的分子机制研究进展[J].中国药理学通报,2024,40(12):2206-2212. doi:10.12360/CPB202306014 . |
| ZHANG W X, ZHOU D Y, HAN Y, et al. Research progress on molecular mechanism underlying neuropsychiatric diseases involving NMDA receptor and α2 adrenergic receptor[J]. Zhongguo Yaolixue Tongbao,2024,40(12):2206-2212. | |
| [35] | 周萌萌,邵坤,匡姝瑜,等. 静脉输注利多卡因发挥镇痛作用的分子机制[J].大连医科大学学报,2024,46(5):450-455. doi:10.11724/jdmu.2024.05.12 . |
| ZHOU M M, SHAO K, KUANG S Y, et al. Molecular mechanisms of analgesic effects of intravenous lidocaine[J]. Dalian Yike Daxue Xuebao,2024,46(5):450-455. | |
| [36] | ARIAS H R. Is the inhibition of nicotinic acetylcholine receptors by bupropion involved in its clinical actions?[J]. Int J Biochem Cell Biol,2009,41(11):2098-2108. doi:10.1016/j.biocel.2009.05.015 . |
| [37] | ZHANG K, YAO Y, HASHIMOTO K. Ketamine and its metabolites: Potential as novel treatments for depression[J]. Neuropharmacology,2023,222:109305. doi:10.1016/j.neuropharm.2022.109305 . |
| [38] | HAMMELMANN V, STIEGLITZ M S, HÜLLE H, et al. Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures[J]. JCI Insight,2019,4(9):e126418. doi:10.1172/jci.insight.126418 . |
| [39] | POSTEA O, BIEL M. Exploring HCN channels as novel drug targets[J]. Nat Rev Drug Discov,2011,10(12):903-914. doi:10.1038/nrd3576 . |
| [40] | DWIVEDI D, BHALLA U S. Physiology and therapeutic potential of SK, H, and M medium afterhyperpolarization ion channels[J]. Front Mol Neurosci,2021,14:658435. doi:10.3389/fnmol.2021.658435 . |
| [41] | PORRO A, SAPONARO A, CASTELLI R, et al. A high affinity switch for cAMP in the HCN pacemaker channels[J]. Nat Commun,2024,15(1):843. doi:10.1038/s41467-024-45136-y . |
| [42] | MCGUIRT A, PIGULEVSKIY I, SULZER D. Developmental regulation of thalamus-driven pauses in striatal cholinergic interneurons[J]. iScience,2022,25(11):105332. doi:10.1016/j.isci.2022.105332 . |
| [43] | CHEN X, SHU S, BAYLISS D A. HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine[J]. J Neurosci,2009,29(3):600-609. doi:10.1523/JNEUROSCI.3481-08.2009 . |
| [44] | HODGKIN A L, HUXLEY A F. Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo[J]. J Physiol,1952,116(4):449-472. doi:10.1113/jphysiol.1952.sp004717 . |
| [45] | KOHTALA S. Ketamine — 50 years in use: From anesthesia to rapid antidepressant effects and neurobiological mechanisms[J]. Pharmacol Rep,2021,73(2):323-345. doi:10.1007/s43440-021-00232-4 . |
| [46] | HESS E M, RIGGS L M, MICHAELIDES M, et al. Mechanisms of ketamine and its metabolites as antidepressants[J]. Biochem Pharmacol,2022,197:114892. doi:10.1016/j.bcp.2021.114892 . |
| [47] | ZHOU Z S, ZHAO Z Q. Ketamine blockage of both tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels of rat dorsal root ganglion neurons[J]. Brain Res Bull,2000,52(5):427-433. doi:10.1016/S0361-9230(00)00283-5 . |
| [48] | WAGNER L E, GINGRICH K J, KULLI J C, et al. Ketamine blockade of voltage-gated sodium channels: Evidence for a shared receptor site with local anesthetics[J]. Anesthesiology,2001,95(6):1406-1413. doi:10.1097/00000542-200112000-00020 . |
| [49] | HAESELER G, TETZLAFF D, BUFLER J, et al. Blockade of voltage-operated neuronal and skeletal muscle sodium channels by S(+)- and R(-)-keta-mine[J]. Anesth Analg,2003,96(4):1019-1026. doi:10.1213/01.ane.0000052513.91900.D5 . |
| [50] | COLECRAFT H M. Designer genetically encoded voltage-dependent calcium channel inhibitors inspired by RGK GTPases[J]. J Physiol,2020,598(9):1683-1693. doi:10.1113/JP276544 . |
| [51] | ROSA P B, BETTIO L E B, NEIS V B, et al. Antidepressant-like effect of guanosine involves activation of AMPA receptor and BDNF/TrkB signaling[J]. Purinergic Signal,2021,17(2):285-301. doi:10.1007/s11302-021-09779-6 . |
| [52] | YAMAKAGE M, HIRSHMAN C A, CROXTON T L. Inhibitory effects of thiopental, ketamine, and propofol on voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells[J]. Anesthesiology,1995,83(6):1274-1282. doi:10.1097/00000542-199 512000-00018 . |
| [53] | DAI Y, ZHANG J H. Role of Cl- current in endothelin-1-induced contraction in rabbit basilar artery[J]. Am J Physiol Heart Circ Physiol,2001,281(5):H2159-H2167. doi:10.1152/ajpheart.2001.281.5.H2159 . |
| [54] | HATAKEYAMA N, YAMAZAKI M, SHIBUYA N, et al. Effects of ketamine on voltage-dependent calcium currents and membrane potentials in single bullfrog atrial cells[J]. J Anesth,2001,15(3):149-153. doi:10.1007/s005400170017 . |
| [55] | CHEN H, VANDORPE D H, XIE X, et al. Disruption of Cav1.2-mediated signaling is a pathway for ketamine-induced pathology[J]. Nat Commun,2020,11(1):4328. doi:10.1038/s41467-020-18167-4 . |
| [56] | DENOMME N, HEIFETS B D. Ketamine, the first associative anesthetic? Some considerations on classifying psychedelics, entactogens, and dissociatives[J]. Am J Psychiatry,2024,181(9):784-786. doi:10.1176/appi.ajp.20240644 . |
| [57] | IQBAL F, THOMPSON A J, RIAZ S, et al. Anesthetics: From modes of action to unconsciousness and neurotoxicity[J]. J Neurophysiol,2019,122(2):760-787. doi:10.1152/jn.00210.2019 . |
| [58] | DAVIS W D, DAVIS K A, HOOPER K. The use of ketamine for the management of acute pain in the emergency department[J]. Adv Emerg Nurs J,2019,41(2):111-121. doi:10.1097/TME.000000000 0000238 . |
| [59] | HIROTA K, KUSHIKATA T. Central noradrenergic neurones and the mechanism of general anaesthesia[J]. Br J Anaesth,2001,87(6):811-813. doi:10.1093/bja/87.6.811 . |
| [60] | KUSHIKATA T, YOSHIDA H, KUDO M, et al. Role of coerulean noradrenergic neurones in general anaesthesia in rats[J]. Br J Anaesth,2011,107(6):924-929. doi:10.1093/bja/aer303 . |
| [61] | STROUS J F M, WEELAND C J, VAN DER DRAAI F A, et al. Brain changes associated with long-term ketamine abuse, a systematic review[J]. Front Neuroanat,2022,16:795231. doi:10.3389/fnana. 2022.795231 . |
| [62] | GE Y, CHEN W, AXERIO-CILIES P, et al. NMDARs in cell survival and death: Implications in stroke pathogenesis and treatment[J]. Trends Mol Med,2020,26(6):533-551. doi:10.1016/j.molmed. 2020.03.001 . |
| [63] | HUANG H, ZHAO C, HU Q, et al. Neonatal anesthesia by ketamine in neonatal rats inhibits the proliferation and differentiation of hippocampal neural stem cells and decreases neurocognitive function in adulthood via inhibition of the Notch1 signaling pathway[J]. Mol Neurobiol,2021,58(12):6272-6289. doi:10.1007/s12035-021-02550-3 . |
| [64] | BEZU L, WU CHUANG A, SAUVAT A, et al. Local anesthetics elicit immune-dependent anticancer effects[J]. J Immunother Cancer,2022,10(4):e004151. doi:10.1136/jitc-2021-004151 . |
| [65] | SPENCER H F, BERMAN R Y, BOESE M, et al. Effects of an intravenous ketamine infusion on inflammatory cytokine levels in male and female Sprague-Dawley rats[J]. J Neuroinflammation,2022,19(1):75. doi:10.1186/s12974-022-02434-w . |
| [66] | SHIBAKAWA Y S, SASAKI Y, GOSHIMA Y, et al. Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide[J]. Br J Anaesth,2005,95(6):803-810. doi:10.1093/bja/aei256 . |
| [67] | SHEHATA I M, KOHAF N A, ELSAYED M W, et al. Ketamine: Pro or antiepileptic agent? A systematic review[J]. Heliyon,2024,10(2):e24433. doi:10.1016/j.heliyon.2024.e24433 . |
| [68] | WANG C, LIU F, PATTERSON T A, et al. Preclinical assessment of ketamine[J]. CNS Neurosci Ther,2013,19(6):448-453. doi:10.1111/cns.12079 . |
| [69] | OLNEY J W, LABRUYERE J, PRICE M T. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs[J]. Science,1989,244(4910):1360-1362. doi:10.1126/science. 2660263 . |
| [70] | JEVTOVIC-TODOROVIC V, WOZNIAK D F, BENSHOFF N D, et al. A comparative evaluation of the neurotoxic properties of ketamine and nitrous oxide[J]. Brain Res,2001,895(1/2):264-267. doi:10.1016/S0006-8993(01)02079-0 . |
| [71] | YANG C, HAN M, ZHANG J C, et al. Loss of parvalbumin-immunoreactivity in mouse brain regions after repeated intermittent administration of esketa-mine, but not R-ketamine[J]. Psychiatry Res,2016,239:281-283. doi:10.1016/j.psychres.2016.03.034 . |
| [72] | ADELL A. Brain NMDA receptors in schizophrenia and depression[J]. Biomolecules,2020,10(6):947. doi:10.3390/biom10060947 . |
| [73] | ZANOS P, MOADDEL R, MORRIS P J, et al. Ketamine and ketamine metabolite pharmacology: Insights into therapeutic mechanisms[J]. Pharmacol Rev,2018,70(3):621-660. doi:10.1124/pr.117.015198 . |
| [74] | KRYSTAL J H, KARPER L P, SEIBYL J P, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses[J]. Arch Gen Psychiatry,1994,51(3):199-214. doi:10.1001/archpsyc.1994.03950030035004 . |
| [75] | FAVA M, FREEMAN M P, FLYNN M, et al. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD)[J]. Mol Psychiatry,2020,25(7):1592-1603. doi:10.1038/s41380-018-0256-5 . |
| [76] | WILLIAMSON D, TURKOZ I, WAJS E, et al. Adverse events and measurement of dissociation after the first dose of esketamine in patients with TRD[J]. Int J Neuropsychopharmacol,2023,26(3):198-206. doi:10.1093/ijnp/pyac081 . |
| [77] | HUA H, HUANG C, LIU H, et al. Depression and antidepressant effects of ketamine and its metabolites: The pivotal role of gut microbiota[J]. Neuropharmacology,2022,220:109272. doi:10.1016/j.neu ropharm.2022.109272 . |
| [78] | SCOTT-HAM M, BURTON F C. Toxicological findings in cases of alleged drug-facilitated sexual assault in the United Kingdom over a 3-year period[J]. J Clin Forensic Med,2005,12(4):175-186. doi:10. 1016/j.jcfm.2005.03.009 . |
| [79] | KALSI S S, WOOD D M, DARGAN P I. The epidemiology and patterns of acute and chronic toxi-city associated with recreational ketamine use[J]. Emerg Health Threats J,2011,4:7107. doi:10.3402/ehtj.v4i0.7107 . |
| [80] | BECK K, HINDLEY G, BORGAN F, et al. Association of ketamine with psychiatric symptoms and implications for its therapeutic use and for understanding schizophrenia: A systematic review and meta-analysis[J]. JAMA Netw Open,2020,3(5):e204693. doi:10.1001/jamanetworkopen.2020.4693 . |
| [81] | YAVI M, LEE H, HENTER I D, et al. Ketamine treatment for depression: A review[J]. Discov Ment Health,2022,2(1):9. doi:10.1007/s44192-022-000 12-3 . |
| [82] | KAMP J, VAN VELZEN M, AARTS L, et al. Stereoselective ketamine effect on cardiac output: A population pharmacokinetic/pharmacodynamic modelling study in healthy volunteers[J]. Br J Anaesth,2021,127(1):23-31. doi:10.1016/j.bja.2021.02.034 . |
| [83] | DOMINO E F, CHODOFF P, CORSSEN G. Pharmacologic effects of CI-581, a new dissociative anesthetic, in man[J]. Clin Pharmacol Ther,1965,6(3):279-291. doi:10.1002/cpt196563279 . |
| [84] | IDVALL J, AHLGREN I, ARONSEN K R, et al. Ketamine infusions: Pharmacokinetics and clinical effects[J]. Br J Anaesth,1979,51(12):1167-1173. doi:10.1093/bja/51.12.1167 . |
| [85] | BOURKE D L, MALIT L A, SMITH T C. Respiratory interactions of ketamine and morphine[J]. Anesthesiology,1987,66(2):153-156. doi:10.1097/00000542-198702000-00008 . |
| [86] | KUMAR A, KOHLI A. Comeback of ketamine: Resurfacing facts and dispelling myths[J]. Korean J Anesthesiol,2021,74(2):103-114. doi:10.4097/kja. 20663 . |
| [87] | RADFORD K D, BERMAN R Y, ZHANG M, et al. Sex-related differences in intravenous ketamine effects on dissociative stereotypy and antinociception in male and female rats[J]. Pharmacol Biochem Behav,2020,199:173042. doi:10.1016/j.pbb.2020.173042 . |
| [88] | MERELMAN A H, PERLMUTTER M C, STRAYER R J. Alternatives to rapid sequence intubation: Contemporary airway management with ketamine[J]. West J Emerg Med,2019,20(3):466-471. doi:10.5811/westjem.2019.4.42753 . |
| [89] | EMERICK T D, MARTIN T J, RIRIE D G. Perio-perative considerations for patients exposed to psychostimulants[J]. Anesth Analg,2023,137(3):474-487. doi:10.1213/ANE.0000000000006303 . |
| [90] | HAO X, YANG Y, LIU J, et al. The modulation by anesthetics and analgesics of respiratory rhythm in the nervous system[J]. Curr Neuropharmacol,2024,22(2):217-240. doi:10.2174/1570159X21666230810110901 . |
| [91] | LI Y, DONG Z, WEN G, et al. Long-term ketamine administration induces bladder damage and upregulates autophagy-associated proteins in bladder smooth muscle tissue[J]. Environ Toxicol,2021,36(12):2521-2529. doi:10.1002/tox.23365 . |
| [92] | SCHEP L J, SLAUGHTER R J, WATTS M, et al. The clinical toxicology of ketamine[J]. Clin Toxicol (Phila),2023,61(6):415-428. doi:10.1080/15563650.2023.2212125 . |
| [93] | ANDERSON D J, ZHOU J, CAO D, et al. Ketamine-induced cystitis: A comprehensive review of the urologic effects of this psychoactive drug[J]. Health Psychol Res,2022,10(3):38247. doi:10.529 65/001c.38247 . |
| [94] | ZHOU L, DUAN J. The role of NMDARs in the anesthetic and antidepressant effects of ketamine[J]. CNS Neurosci Ther,2024,30(4):e14464. doi:10.11 11/cns.14464 . |
| [95] | LV Q, YANG L, LI G, et al. Large-scale persistent network reconfiguration induced by ketamine in anesthetized monkeys: Relevance to mood disorders[J]. Biol Psychiatry,2016,79(9):765-775. doi:10.1016/j.biopsych.2015.02.028 . |
| [96] | FOX M E, LOBO M K. The molecular and cellular mechanisms of depression: A focus on reward circuitry[J]. Mol Psychiatry,2019,24(12):1798-1815. doi:10.1038/s41380-019-0415-3 . |
| [97] | SIMMLER L D, LI Y, HADJAS L C, et al. Dual action of ketamine confines addiction liability[J]. Nature,2022,608(7922):368-373. doi:10.1038/s415 86-022-04993-7 . |
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