Esketamine/Ketamine: Dual‐Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology
Source abstract
Abstract
Abstract Esketamine and ketamine are perioperative analgesics and anesthetics that have been widely adopted in clinical practice in Europe and the United States. However, their application in China remains in the early stages of exploration and implementation. Esketamine and ketamine exert their effects through multiple receptors and pathways, but primarily act through non‐competitive antagonism of the N‐methyl‐D‐aspartate receptor (NMDAR). However, due to their potential side effects and addictive properties, they are subject to certain regulatory controls and are not readily included in routine pharmaceutical use. This review meticulously and systematically synthesizes the latest research progress on Esketamine and ketamine. Their classical applications, including analgesia, sedation, and anesthesia, as well as antidepressant, anti‐tumor, and anti‐inflammatory effects, are comprehensively covered. By integrating findings from both preclinical and clinical investigations and taking into full account potential limitations, this review aims to provide profound insights that can effectively inform the clinical utilization and future research directions of ketamine and esketamine as versatile therapeutic agents.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Treatment of Major Depression · Cancer, Stress, Anesthesia, and Immune Response · Anesthesia and Neurotoxicity Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
School of Medicine Nankai University Tianjin 300071 China
The Institute of Translational Medicine Tianjin Cancer Institute of Integrative Traditional Chinese and Western Medicine Tianjin Union Medical Center The First Affiliated Hospital of Nankai University Nankai University Tianjin 300121 China
Department of Anesthesiology Tianjin Union Medical Center The First Affiliated Hospital of Nankai University Nankai University Tianjin 300121 China
Department of Anesthesiology Tianjin Central Hospital of Gynaecology Obsterics Nankai University Tianjin 300071 China
Department of Anesthesiology Tianjin First Central Hospital Tianjin 300110 China
Key Laboratory of Functional Polymer Materials of Ministry of Education College of Chemistry State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for New Organic Matter Nankai University Tianjin 300071 China
Funding
Natural Science Foundation of Tianjin Municipal Science and Technology Commission · Tianjin Municipal Transportation Commission Science and Technology Development Plan Project
References (100+)
Show source-provided references
1. 10.1016/j.neuropharm.2022.10917110.1016/j.neuropharm.2022.109171 ↗
2. 10.1097/ALN.0b013e3181ed09a210.1097/ALN.0b013e3181ed09a2 ↗
3. 10.1002/ibra.1209410.1002/ibra.12094 ↗
4. 10.1016/S0006-3223(99)00230-910.1016/S0006-3223(99)00230-9 ↗
5. 10.1016/S2215-0366(19)30394-310.1016/S2215-0366(19)30394-3 ↗
6. 10.5811/westjem.2019.4.4275310.5811/westjem.2019.4.42753 ↗
7. 10.1097/TME.000000000000022210.1097/TME.0000000000000222 ↗
8. 10.1016/j.bja.2023.11.03010.1016/j.bja.2023.11.030 ↗
9. 10.1038/s41467-023-37463-310.1038/s41467-023-37463-3 ↗
10. 10.1016/j.ajem.2023.12.04110.1016/j.ajem.2023.12.041 ↗
11. 10.1124/pr.117.01519810.1124/pr.117.015198 ↗
12. 10.1002/da.2253610.1002/da.22536 ↗
13. 10.2147/SAR.S1545810.2147/SAR.S15458 ↗
14. 10.1016/j.bja.2018.02.02110.1016/j.bja.2018.02.021 ↗
15. 10.1016/j.jad.2018.02.02510.1016/j.jad.2018.02.025 ↗
16. 10.1097/00000542-198003000-0000810.1097/00000542-198003000-00008 ↗
17. 10.1016/j.jclinane.2020.11007110.1016/j.jclinane.2020.110071 ↗
18. 10.1016/j.bja.2021.03.01710.1016/j.bja.2021.03.017 ↗
19. 10.1007/s00101005050310.1007/s001010050503 ↗
20. 10.1016/j.anclin.2023.03.00510.1016/j.anclin.2023.03.005 ↗
21. 10.1007/s43440-021-00232-410.1007/s43440-021-00232-4 ↗
22. 10.1016/S0009-9236(01)06321-410.1016/S0009-9236(01)06321-4 ↗
23. 10.1038/s41380-021-01093-210.1038/s41380-021-01093-2 ↗
24. 10.1097/ACO.000000000000091610.1097/ACO.0000000000000916 ↗
25. 10.1016/j.ejphar.2019.17254710.1016/j.ejphar.2019.172547 ↗
26. 10.3390/cells1104064510.3390/cells11040645 ↗
27. 10.1002/cpt.347810.1002/cpt.3478 ↗
28. 10.1016/j.drudis.2023.10351810.1016/j.drudis.2023.103518 ↗
29. 10.1016/j.jad.2022.03.07210.1016/j.jad.2022.03.072 ↗
30. 10.1111/j.1600-0714.2004.00226.x10.1111/j.1600-0714.2004.00226.x ↗
31. 10.1186/s12871-015-0076-y10.1186/s12871-015-0076-y ↗
32. 10.1186/1471-2407-13-46810.1186/1471-2407-13-468 ↗
33. 10.1007/s00232-005-0777-010.1007/s00232-005-0777-0 ↗
34. 10.1002/ijc.2293410.1002/ijc.22934 ↗
35. 10.1097/00000542-200110000-0002210.1097/00000542-200110000-00022 ↗
36. 10.1213/00000539-199909000-0002410.1213/00000539-199909000-00024 ↗
37. 10.1097/00000542-199402000-0002010.1097/00000542-199402000-00020 ↗
38. 10.1007/BF0301670110.1007/BF03016701 ↗
39. 10.1051/vetres:200406110.1051/vetres:2004061 ↗
40. 10.1016/j.lfs.2025.12359410.1016/j.lfs.2025.123594 ↗
41. 10.1097/MD.000000000004296210.1097/MD.0000000000042962 ↗
42. 10.1016/j.psc.2023.02.00310.1016/j.psc.2023.02.003 ↗
43. 10.1177/026988112095964410.1177/0269881120959644 ↗
44. 10.1111/j.1460-9568.2011.07628.x10.1111/j.1460-9568.2011.07628.x ↗
45. 10.1016/j.neuropharm.2013.03.03010.1016/j.neuropharm.2013.03.030 ↗
46. 10.1213/01.ANE.0000081061.12235.5510.1213/01.ANE.0000081061.12235.55 ↗
47. 10.1111/cns.1209910.1111/cns.12099 ↗
48. 10.1007/s11916-000-0070-y10.1007/s11916-000-0070-y ↗
49. 10.1016/j.niox.2011.11.00310.1016/j.niox.2011.11.003 ↗
50. 10.1186/s12974-020-1703-110.1186/s12974-020-1703-1 ↗
51. Xue M. · Oxid Med. Cell Longev. · 2020 · 7
52. 10.1007/s10787-014-0213-010.1007/s10787-014-0213-0 ↗
53. 10.1248/bpb.34.117010.1248/bpb.34.1170 ↗
54. 10.1111/j.1469-7793.2001.0115k.x10.1111/j.1469-7793.2001.0115k.x ↗
55. 10.1097/00000542-200501000-0003010.1097/00000542-200501000-00030 ↗
56. 10.1016/S0306-4522(00)00193-710.1016/S0306-4522(00)00193-7 ↗
57. 10.1097/00001756-200110290-0002210.1097/00001756-200110290-00022 ↗
58. 10.1097/00000539-200112000-0003110.1097/00000539-200112000-00031 ↗
59. 10.1016/j.ejphar.2019.17280810.1016/j.ejphar.2019.172808 ↗
60. 10.1016/j.neuroscience.2007.04.03010.1016/j.neuroscience.2007.04.030 ↗
61. 10.1097/ALN.0b013e3181a105de10.1097/ALN.0b013e3181a105de ↗
62. 10.1111/bcp.1209410.1111/bcp.12094 ↗
63. 10.1016/j.brainres.2005.11.05410.1016/j.brainres.2005.11.054 ↗
64. 10.1213/ANE.0b013e3181bdc8a010.1213/ANE.0b013e3181bdc8a0 ↗
65. 10.1016/j.celrep.2021.10997810.1016/j.celrep.2021.109978 ↗
66. 10.1038/s41467-018-06295-x10.1038/s41467-018-06295-x ↗
67. 10.1016/j.pain.2009.08.01510.1016/j.pain.2009.08.015 ↗
68. 10.1016/j.ejpain.2010.06.01610.1016/j.ejpain.2010.06.016 ↗
69. 10.1021/jm00161a04310.1021/jm00161a043 ↗
70. 10.1517/17425255.2012.71268610.1517/17425255.2012.712686 ↗
71. 10.1016/j.pbb.2008.05.01110.1016/j.pbb.2008.05.011 ↗
72. 10.1016/S0014-2999(97)01116-310.1016/S0014-2999(97)01116-3 ↗
73. 10.1136/rapm-2018-00001310.1136/rapm-2018-000013 ↗
74. 10.1111/j.1460-9592.2007.02257.x10.1111/j.1460-9592.2007.02257.x ↗
75. 10.1097/ALN.0b013e31825b6c9110.1097/ALN.0b013e31825b6c91 ↗
76. 10.1523/JNEUROSCI.4152-11.201110.1523/JNEUROSCI.4152-11.2011 ↗
77. 10.1016/j.ejpain.2011.03.00810.1016/j.ejpain.2011.03.008 ↗
78. 10.1097/AAP.000000000000075610.1097/AAP.0000000000000756 ↗
79. 10.1113/jphysiol.2013.27005810.1113/jphysiol.2013.270058 ↗
80. 10.1523/JNEUROSCI.3481-08.200910.1523/JNEUROSCI.3481-08.2009 ↗
81. 10.1097/ALN.0b013e318287b7c810.1097/ALN.0b013e318287b7c8 ↗
82. 10.18632/oncotarget.2440810.18632/oncotarget.24408 ↗
83. 10.1016/j.tacc.2014.03.00210.1016/j.tacc.2014.03.002 ↗
84. 10.1016/j.annemergmed.2021.05.02310.1016/j.annemergmed.2021.05.023 ↗
85. Maghraby N. · Arch. Acad. Emerg. Med. · 2025 · 13
86. 10.1097/EJA.000000000000113410.1097/EJA.0000000000001134 ↗
87. 10.1038/s41586-021-03769-910.1038/s41586-021-03769-9 ↗
88. 10.1097/00000542-200203000-0002310.1097/00000542-200203000-00023 ↗
89. 10.1093/bja/69.3.29210.1093/bja/69.3.292 ↗
90. 10.1111/anae.1564110.1111/anae.15641 ↗
91. 10.1172/JCI13080810.1172/JCI130808 ↗
92. 10.1038/nature1799810.1038/nature17998 ↗
93. 10.1097/MD.000000000003162410.1097/MD.0000000000031624 ↗
94. 10.1016/j.injury.2020.12.03310.1016/j.injury.2020.12.033 ↗
95. Lou F. · Altern. Ther. Health. Med. · 2023 · 29 · 424
96. Tu W. · Am. J. Transl. Res. · 2021 · 13 · 1701
97. 10.1111/jcpt.1360410.1111/jcpt.13604 ↗
98. 10.2147/DDDT.S22455310.2147/DDDT.S224553 ↗
99. 10.1111/bcp.1572610.1111/bcp.15726 ↗
100. 10.1007/s11695-023-06676-210.1007/s11695-023-06676-2 ↗