Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels.
Pain
analgesics
central nervous system
ion channels
peripheral nervous system
potassium channels
Journal
Current neuropharmacology
ISSN: 1875-6190
Titre abrégé: Curr Neuropharmacol
Pays: United Arab Emirates
ID NLM: 101157239
Informations de publication
Date de publication:
2022
2022
Historique:
received:
05
01
2021
revised:
14
03
2021
accepted:
24
03
2021
pubmed:
9
4
2021
medline:
27
1
2022
entrez:
8
4
2021
Statut:
ppublish
Résumé
Two-pore domain potassium (K2P) channels are a diverse family of potassium channels. K2P channels generate background leak potassium currents to regulate cellular excitability and are thereby involved in a wide range of neurological disorders. K2P channels are modulated by a variety of physicochemical factors, such as mechanical stretch, temperature, and pH. In the peripheral nervous system, K2P channels are widely expressed in nociceptive neurons and play a critical role in pain perception. In this review, we summarize the recent advances in the pharmacological properties of K2P channels, with a focus on the exogenous small-molecule activators targeting K2P channels. We emphasize the subtype-selectivity, cellular and in vivo pharmacological properties of all the reported small-molecule activators. The key underlying analgesic mechanisms mediated by K2P are also summarized based on the data in the literature from studies using small-molecule activators and genetic knock-out animals. We discuss the advantages and limitations of the translational perspectives of K2P in pain medicine and provide outstanding questions for future studies in the end.
Identifiants
pubmed: 33827408
pii: CN-EPUB-115241
doi: 10.2174/1570159X19666210407152528
pmc: PMC9199554
doi:
Substances chimiques
Analgesics, Non-Narcotic
0
Potassium Channels, Tandem Pore Domain
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
16-26Subventions
Organisme : National Natural Science Foundation of China
ID : 32071003, 81873808
Organisme : 1.3.5 Project for Disciplines of Excellence of West China Hospital of Sichuan University
ID : ZY2016101
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Références
Pharmacol Rev. 2015 Oct;67(4):821-70
pubmed: 26362469
EMBO Mol Med. 2011 May;3(5):266-78
pubmed: 21438154
Front Pharmacol. 2013 May 15;4:63
pubmed: 23720627
J Physiol. 2013 Dec 1;591(23):5977-98
pubmed: 24042502
Neurochem Res. 2017 May;42(5):1288-1298
pubmed: 28160200
Adv Exp Med Biol. 2018;1099:37-47
pubmed: 30306513
J Neurosci. 2014 Jan 22;34(4):1494-509
pubmed: 24453337
Pain. 2008 May;136(1-2):202-10
pubmed: 18337008
EMBO J. 1996 Mar 1;15(5):1004-11
pubmed: 8605869
Pharmacol Ther. 2013 May;138(2):272-84
pubmed: 23356979
Br J Pharmacol. 2018 Jun;175(12):2272-2283
pubmed: 29150838
Lancet. 2013 Jun 8;381(9882):1987-2015
pubmed: 23746901
Biochem Biophys Res Commun. 2013 Nov 15;441(2):463-8
pubmed: 24383077
Biochem Biophys Res Commun. 2001 Jun 22;284(4):923-30
pubmed: 11409881
Neurochem Res. 2018 Jun;43(6):1143-1149
pubmed: 29736614
J Pharmacol Exp Ther. 2005 Apr;313(1):250-9
pubmed: 15608074
Br J Pharmacol. 2018 Jun;175(12):2185-2203
pubmed: 28924972
Proc Natl Acad Sci U S A. 2020 Jun 16;117(24):13757-13766
pubmed: 32467161
Br J Pharmacol. 2020 Oct;177(20):4782-4795
pubmed: 32851651
Nat Commun. 2017 Aug 29;8(1):378
pubmed: 28851868
Eur J Med Chem. 2014 Mar 21;75:391-402
pubmed: 24561669
Int J Mol Sci. 2019 May 20;20(10):
pubmed: 31137507
Pflugers Arch. 2015 May;467(5):907-16
pubmed: 25482669
Nat Neurosci. 2014 Oct;17(10):1304-12
pubmed: 25254980
Mol Pharmacol. 2014 May;85(5):671-81
pubmed: 24509840
Lancet. 2019 Sep 28;394(10204):1145-1158
pubmed: 31248666
Pain. 2014 Dec;155(12):2534-2544
pubmed: 25239074
J Biol Chem. 2001 Mar 9;276(10):7302-11
pubmed: 11060316
Mol Cell Neurosci. 2012 Mar;49(3):375-86
pubmed: 22273507
EMBO J. 1996 Dec 16;15(24):6854-62
pubmed: 9003761
J Biol Chem. 2000 Jun 9;275(23):17412-9
pubmed: 10747911
Front Mol Neurosci. 2019 Jul 17;12:170
pubmed: 31379497
Physiol Rev. 2010 Apr;90(2):559-605
pubmed: 20393194
Basic Res Cardiol. 2017 Jan;112(1):8
pubmed: 28005193
Mol Psychiatry. 2021 Mar;26(3):941-954
pubmed: 30980042
Mol Cell Neurosci. 2017 Sep;83:13-26
pubmed: 28676376
Science. 2012 Jan 27;335(6067):436-41
pubmed: 22282805
Nat Rev Drug Discov. 2017 Aug;16(8):545-564
pubmed: 28596533
Mol Pharmacol. 2019 Jul;96(1):26-35
pubmed: 31015283
ACS Chem Neurosci. 2018 Dec 19;9(12):3153-3165
pubmed: 30089357
Neuron. 2018 Jan 17;97(2):299-312.e6
pubmed: 29290552
Am J Hum Genet. 2008 Aug;83(2):193-9
pubmed: 18678320
EMBO J. 1997 Sep 1;16(17):5464-71
pubmed: 9312005
J Biol Chem. 2003 Jul 25;278(30):27406-12
pubmed: 12754259
Science. 2015 Mar 13;347(6227):1256-9
pubmed: 25766236
J Biol Chem. 2016 Jun 24;291(26):13649-61
pubmed: 27129242
Biochem Biophys Res Commun. 2004 Oct 8;323(1):323-31
pubmed: 15351740
J Clin Invest. 2018 Nov 1;128(11):4843-4855
pubmed: 30153110
Clin Drug Investig. 2012 Feb 22;32 Suppl 1:53-63
pubmed: 22356224
J Physiol. 2020 Mar;598(5):1017-1038
pubmed: 31919847
Nat Neurosci. 2006 Sep;9(9):1134-41
pubmed: 16906152
Pflugers Arch. 2015 May;467(5):931-43
pubmed: 25420526
Nat Commun. 2014;5:3227
pubmed: 24496152
ACS Chem Neurosci. 2017 Mar 15;8(3):558-568
pubmed: 27805811
Nat Commun. 2013;4:2941
pubmed: 24346231
Pain. 2019 Jan;160(1):28-37
pubmed: 30586068
Pain Physician. 2008 Mar;11(2 Suppl):S105-20
pubmed: 18443635
Science. 2012 Jan 27;335(6067):432-6
pubmed: 22282804
EMBO J. 2009 May 6;28(9):1308-18
pubmed: 19279663
J Biol Chem. 2014 Oct 10;289(41):28202-12
pubmed: 25148687
Br J Pharmacol. 2019 Jan;176(2):256-266
pubmed: 30325008
Br J Pharmacol. 2013 Mar;168(5):1240-54
pubmed: 23072356
Brain Res. 2011 Oct 6;1416:69-79
pubmed: 21885038
Mol Pharmacol. 2012 Mar;81(3):393-400
pubmed: 22147752
Mol Cell Neurosci. 2013 Nov;57:1-9
pubmed: 23994814
Biochem Biophys Res Commun. 2001 Mar 23;282(1):249-56
pubmed: 11263999
Mol Pain. 2011 Apr 28;7:30
pubmed: 21527011
Front Mol Neurosci. 2012 Mar 05;5:21
pubmed: 22403526
Biochem Biophys Res Commun. 2017 Nov 4;493(1):444-450
pubmed: 28882594
Mol Pharmacol. 2004 Mar;65(3):599-610
pubmed: 14978238
Pain. 2020 Sep 1;161(9):1976-1982
pubmed: 32694387
PLoS One. 2017 Oct 10;12(10):e0186252
pubmed: 29016681
Anesthesiology. 2010 Dec;113(6):1326-37
pubmed: 21042202
Am J Physiol Cell Physiol. 2006 Jul;291(1):C138-46
pubmed: 16495368
Physiol Rev. 2019 Apr 1;99(2):1079-1151
pubmed: 30672368
Sci Transl Med. 2019 Nov 20;11(519):
pubmed: 31748231
Sci Rep. 2016 Feb 16;6:21248
pubmed: 26879043
Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17546-51
pubmed: 19805135
Neuroscience. 2016 Dec 17;339:622-633
pubmed: 27789381
Sci Signal. 2012 Nov 20;5(251):ra84
pubmed: 23169818
Lancet. 2013 Aug 31;382(9894):769-79
pubmed: 23726390
J Biol Chem. 2002 Feb 15;277(7):5426-32
pubmed: 11733509
Cell. 2016 Feb 25;164(5):937-49
pubmed: 26919430
J Neurosci. 2009 Jul 1;29(26):8551-64
pubmed: 19571146
Biochem Biophys Res Commun. 2017 Aug 26;490(3):1125-1131
pubmed: 28676394
J Med Chem. 2020 Apr 9;63(7):3665-3677
pubmed: 32162512
Respir Physiol. 2001 Dec;129(1-2):159-74
pubmed: 11738652
Endocrinology. 2014 Oct;155(10):3757-68
pubmed: 24932805
J Biol Chem. 2000 Jun 2;275(22):16650-7
pubmed: 10747866
J Biol Chem. 2000 Sep 15;275(37):28398-405
pubmed: 10880510
Pflugers Arch. 2014 Jul;466(7):1289-300
pubmed: 24081450
Cell Rep. 2014 Sep 11;8(5):1571-82
pubmed: 25199828
Biomol Ther (Seoul). 2016 May 1;24(3):252-9
pubmed: 27133259
J Neurosci. 2004 Jul 28;24(30):6693-702
pubmed: 15282272
J Physiol. 2007 Jan 15;578(Pt 2):377-85
pubmed: 17068099
J Biol Chem. 2004 Apr 30;279(18):18550-8
pubmed: 14981085
J Physiol. 2007 Dec 15;585(Pt 3):867-79
pubmed: 17962323
Eur J Pharmacol. 2019 Nov 5;862:172631
pubmed: 31472119
EMBO J. 2004 Jul 7;23(13):2684-95
pubmed: 15175651
Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:401-420
pubmed: 32679007
Science. 2019 Feb 22;363(6429):875-880
pubmed: 30792303
Neuron. 2019 Dec 4;104(5):960-971.e7
pubmed: 31630908
Brain Res Bull. 2018 Jan;136:26-36
pubmed: 27965079
Neuroscience. 2015 Aug 6;300:85-93
pubmed: 25982558
Eur J Pharmacol. 2014 Oct 5;740:603-10
pubmed: 24972239
Eur J Pharmacol. 2014 Sep 5;738:250-5
pubmed: 24927994
EMBO J. 2006 Jun 7;25(11):2368-76
pubmed: 16675954
Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4194-9
pubmed: 27035963
J Pharmacol Exp Ther. 2006 May;317(2):615-26
pubmed: 16397088
Respir Physiol Neurobiol. 2007 Jul 1;157(1):55-64
pubmed: 17416212
Trends Neurosci. 2014 Mar;37(3):146-58
pubmed: 24461875
Science. 2016 Nov 4;354(6312):572-577
pubmed: 27811267
Pharmacol Rev. 2005 Dec;57(4):527-40
pubmed: 16382106
Neuroreport. 2013 Feb 13;24(3):131-6
pubmed: 23370493
J Med Chem. 2017 Feb 9;60(3):1076-1088
pubmed: 28051863
Yonsei Med J. 2015 Sep;56(5):1307-15
pubmed: 26256973
EMBO J. 1998 Jun 15;17(12):3297-308
pubmed: 9628867
Sci Signal. 2018 Oct 16;11(552):
pubmed: 30327410
ACS Chem Biol. 2013 Aug 16;8(8):1841-51
pubmed: 23738709
Neuron. 2019 Jan 16;101(2):232-245.e6
pubmed: 30573346
Diabetes. 2015 Nov;64(11):3818-28
pubmed: 26239056
Nat Commun. 2015 Dec 04;6:8967
pubmed: 26634308
Eur J Pain. 2013 Nov;17(10):1547-57
pubmed: 23720357
J Comp Neurol. 2016 Jun 1;524(8):1646-52
pubmed: 26788716
Nature. 2017 Jul 20;547(7663):364-368
pubmed: 28693035
Nat Med. 2010 Oct;16(10):1157-60
pubmed: 20871611
Bioorg Med Chem Lett. 2019 Jul 1;29(13):1601-1604
pubmed: 31072652
Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4200-5
pubmed: 27035965