View source for Potassium channel blocker

{{short description|Several medications that disrupt movement of K+ ions}}
{{refimprove|date=June 2019}}
[[File:Tetraethylammonium.svg|thumb|250px|[[Tetraethylammonium]] is a commonly used potassium channel blocker]]
'''Potassium channel blockers''' are agents which interfere with conduction through [[potassium channel]]s.
== Medical uses ==
=== Arrhythmia ===
[[Image:Action potential Class III.svg|thumb|275px|Effect of class III antiarrhythmic agent on cardiac action potential.]]
Potassium channel blockers used in the treatment of [[cardiac arrhythmia]] are classified as class III antiarrhythmic agents. Atrial cardiomyocytes contain a specific subset of potassium ion channels which are absent in the ventricles.<ref name="pmid27261831">{{cite journal | vauthors=Voigt N, Dobrev D | title=Atrial-Selective Potassium Channel Blockers | journal=Cardiac Electrophysiology Clinics | volume=8| issue=2 | pages=411-421- | year=2016 |  doi = 10.1016/j.ccep.2016.02.005 | pmid=27261831  }}</ref> Safety and efficacy of anti-arrhythmic potassium channel blockers will be improved by discovery of blockers specific to atria or ventricle.<ref name="pmid27261831" />
====Mechanism====
Class III agents predominantly block the potassium channels, thereby prolonging repolarization.<ref name="pmid10907968">{{cite journal |vauthors=Lenz TL, Hilleman DE |title=Dofetilide, a new class III antiarrhythmic agent |journal=Pharmacotherapy |volume=20 |issue=7 |pages=776–86 |date=July 2000 |pmid=10907968 |doi= 10.1592/phco.20.9.776.35208|s2cid=19897963 }}</ref> More specifically, their primary effect is on [[HERG|I<sub>Kr</sub>]].<ref name="pmid18651412">{{cite journal  |vauthors=Riera AR, Uchida AH, Ferreira C, etal |title=Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome |journal=Cardiol J |volume=15 |issue=3 |pages=209–19 |year=2008 |pmid=18651412 }}</ref>
Since these agents do not affect the [[sodium channel]], conduction velocity is not decreased.  The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is less likely to interact with tissue that has become refractory).
====Examples and uses====
*[[Amiodarone]] is indicated for the treatment of refractory [[Ventricular tachycardia|VT]] or [[Ventricular fibrillation|VF]], particularly in the setting of acute ischemia.  Amiodarone is also safe to use in individuals with [[cardiomyopathy]] and [[atrial fibrillation]], to maintain normal sinus rhythm. Amiodarone prolongation of the action potential is uniform over a wide range of heart rates, so this drug does '''not''' have reverse use-dependent action.  [[Amiodarone]] was the first agent described in this class.<ref>{{cite web |url=http://www.medscape.com/viewarticle/412798_3 |title=Milestones in the Evolution of the Study of Arrhythmias }}</ref>   Amiodarone should only be used to treat adults with life-threatening ventricular arrhythmias when other treatments are ineffective or have not been tolerated.<ref>{{cite web|title=FDA MedWatch|website=[[Food and Drug Administration]]|url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm084108.htm}}</ref>
* [[Dofetilide]] blocks only the rapid K channels; this means that at higher heart rates, when there is increased involvement of the slow K channels, dofetilide has less of an action potential-prolonging effect.
* [[Sotalol]] is indicated for the treatment of atrial or ventricular tachyarrhythmias, and [[AV re-entrant arrhythmia]]s.
* [[Ibutilide]] is the only antiarrhythmic agent currently approved by the [[Food and Drug Administration]] for acute conversion of [[atrial fibrillation]] to sinus rhythm.
* [[Azimilide]]
* [[Bretylium]]
* [[Clofilium]]
* [[E-4031]]
* [[Nifekalant]]<ref name="pmid12890916">{{cite journal |vauthors=Sahara M, Sagara K, Yamashita T, Iinuma H, Fu LT, Watanabe H |title=Nifekalant hydrochloride, a novel class III antiarrhythmic agent, suppressed postoperative recurrent ventricular tachycardia in a patient undergoing coronary artery bypass grafting and the Dor approach |journal=Circ. J. |volume=67 |issue=8 |pages=712–4 |date=August 2003 |pmid=12890916 |doi= 10.1253/circj.67.712|s2cid=44536952 |url=http://www.jstage.jst.go.jp/article/circj/67/8/67_712/_article/-char/en|doi-access=free }}</ref>
* [[Tedisamil]]
* [[Sematilide]]
====Side effects====
These agents include a risk of [[torsades de pointes]].<ref name="urlIntroduction: Arrhythmias and Conduction Disorders: Merck Manual Professional">{{cite web |url=http://www.merck.com/mmpe/sec07/ch075/ch075a.html |title=Introduction: Arrhythmias and Conduction Disorders: Merck Manual Professional }}</ref>
===Anti-diabetics===
[[Sulfonylureas]], such as [[gliclazide]], are [[ATP-sensitive potassium channel]] blockers.
===Other uses===
[[Dalfampridine]], A potassium channel blocker has also been approved for use in the treatment of [[multiple sclerosis]].<ref name="pmid16472864">{{cite journal |vauthors=Judge SI, Bever CT |title=Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment |journal=Pharmacol. Ther. |volume=111 |issue=1 |pages=224–59 |date=July 2006 |pmid=16472864 |doi=10.1016/j.pharmthera.2005.10.006 }}</ref>
A study appears to indicate that topical spray of a selective Tandem pore Acid-Sensitive K+  (TASK 1/3 K+) (potassium antagonist) increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and obstructive sleep apnoea (OSA). <ref>[https://news.flinders.edu.au/blog/2024/03/15/sleep-apnea-solution-could-be-right-under-your-nose/ Flinders unu,UA:Sleep apnea solution could be right under your nose]</ref> <ref> [https://pubmed.ncbi.nlm.nih.gov/32472332/ NIH PubMed:TASK channels: channelopathies, trafficking, and receptor-mediated inhibition]</ref>
== Reverse use dependence ==
Potassium channel blockers exhibit reverse use-dependent prolongation of the action potential duration. Reverse use dependence is the effect where the efficacy of the drug is reduced after repeated use of the tissue.<ref name=":0">{{Citation|last=Hondeghem|first=L. M.|title=Use Dependence and Reverse Use Dependence of Antiarrhythmic Agents: Pro- and Antiarrhythmic Actions|date=1995|work=Antiarrhythmic Drugs: Mechanisms of Antiarrhythmic and Proarrhythmic Actions|pages=92–105|editor-last=Breithardt|editor-first=Günter|publisher=Springer Berlin Heidelberg|doi=10.1007/978-3-642-85624-2_6|isbn=9783642856242|editor2-last=Borggrefe|editor2-first=Martin|editor3-last=Camm|editor3-first=A. John|editor4-last=Shenasa|editor4-first=Mohammad}}</ref> This contrasts with (ordinary) use dependence, where the efficacy of the drug is increased after repeated use of the tissue.
Reverse use dependence is relevant for potassium channel blockers used as class III antiarrhythmics. Reverse use dependent drugs that slow heart rate (such as [[quinidine]]) can be less effective at high heart rates.<ref name=":0" /> The [[Refractory period (physiology)|refractoriness]] of the ventricular [[myocyte]] increases at lower [[heart rate]]s.{{Citation needed|date=June 2019}}  This increases the susceptibility of the myocardium to [[early Afterdepolarizations]] (EADs) at low heart rates.{{Citation needed|date=June 2019}} Antiarrhythmic agents that exhibit reverse use-dependence (such as [[quinidine]]) are more efficacious at preventing a tachyarrhythmia than converting someone into normal sinus rhythm.{{Citation needed|date=June 2019}} Because of the reverse use-dependence of class III agents, at low heart rates class III antiarrhythmic agents may paradoxically be more arrhythmogenic.
Drugs such as quinidine may be both reverse use dependent and use dependent.<ref name=":0" />
== Calcium-activated potassium channel blockers ==
Examples of [[Calcium-activated potassium channel|calcium-activated potassium]] channel blockers include:
*[[Charybdotoxin]]<ref name="pmid10777734">{{cite journal | vauthors = Thompson J, Begenisich T | title = Electrostatic interaction between charybdotoxin and a tetrameric mutant of Shaker K(+) channels | journal = Biophysical Journal | volume = 78 | issue = 5 | pages = 2382–91 | date = May 2000 | pmid = 10777734 | pmc = 1300827 | doi = 10.1016/S0006-3495(00)76782-8 | bibcode = 2000BpJ....78.2382T }}</ref><ref name="pmid8562075">{{cite journal | vauthors = Naranjo D, Miller C | title = A strongly interacting pair of residues on the contact surface of charybdotoxin and a Shaker K+ channel | journal = Neuron | volume = 16 | issue = 1 | pages = 123–30 | date = January 1996 | pmid = 8562075 | doi = 10.1016/S0896-6273(00)80029-X | s2cid = 16794677 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yu M, Liu SL, Sun PB, Pan H, Tian CL, Zhang LH | title = Peptide toxins and small-molecule blockers of BK channels | journal = Acta Pharmacologica Sinica | volume = 37 | issue = 1 | pages = 56–66 | date = January 2016 | pmid = 26725735 | pmc = 4722972 | doi = 10.1038/aps.2015.139 }}</ref><ref name="Rang60">{{cite book|title=Pharmacology|author=Rang, HP|publisher=Churchill Livingstone|year=2015|isbn=978-0-443-07145-4|edition=8|location=Edinburgh|page=59}}</ref>
* [[Iberiotoxin]]<ref name="Candia 1992">{{cite journal | last1 = Candia | first1 = S | last2 = Garcia | first2 = ML | last3 = Latorre | first3 = R | title = Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)-activated K+ channel | journal = Biophysical Journal | volume = 63 | issue = 2 | pages = 583–90 | year = 1992 | pmid = 1384740 | pmc = 1262182 | doi = 10.1016/S0006-3495(92)81630-2 | bibcode=1992BpJ....63..583C}}</ref>
*[[Apamin]]<ref name="Stocker 1999">{{cite journal|title= An apamin-sentisitive Ca<sup>2+</sup>-activated K<sup>+</sup> current in hippocampal pyramidal neurons |author1=M. Stocker |author2=M. Krause |author3=P. Pedarzani | journal = PNAS | volume = 96 | issue = 8 |pages= 4662–4667 | year = 1999 | doi= 10.1073/pnas.96.8.4662 |pmid= 10200319 |pmc=16389 |bibcode= 1999PNAS...96.4662S |doi-access=free }}</ref><ref name="Rang60" />
*[[Kaliotoxin]],<ref>{{Cite journal|last1=Baldus|first1=Marc|last2=Becker|first2=Stefan|last3=Pongs|first3=Olaf|last4=Martin-Eauclaire|first4=Marie-France|last5=Hornig|first5=Sönke|last6=Giller|first6=Karin|last7=Lange|first7=Adam|date=April 2006|title=Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR|journal=Nature|volume=440|issue=7086|pages=959–962|doi=10.1038/nature04649|pmid=16612389|issn=1476-4687|bibcode=2006Natur.440..959L|s2cid=4429604}}</ref><ref>{{Cite journal|last1=Martin-Eauclaire|first1=M. F.|last2=Mansuelle|first2=P.|last3=Rochat|first3=H.|last4=Benslimane|first4=A.|last5=Zerrouk|first5=H.|last6=Gola|first6=M.|last7=Jacquet|first7=G.|last8=Crest|first8=M.|date=1992-01-25|title=Kaliotoxin, a novel peptidyl inhibitor of neuronal BK-type Ca(2+)-activated K+ channels characterized from Androctonus mauretanicus mauretanicus venom.|url=http://www.jbc.org/content/267/3/1640|journal=Journal of Biological Chemistry|volume=267|issue=3|pages=1640–1647|doi=10.1016/S0021-9258(18)45993-5|issn=0021-9258|pmid=1730708|doi-access=free}}</ref>
*[[Lolitrem B|Lolitrem]],<ref name="2016rev">{{cite journal|last1=Philippe|first1=G|date=15 February 2016|title=Lolitrem B and Indole Diterpene Alkaloids Produced by Endophytic Fungi of the Genus Epichloë and Their Toxic Effects in Livestock.|journal=Toxins|volume=8|issue=2|pages=47|doi=10.3390/toxins8020047|pmc=4773800|pmid=26891327|doi-access=free}}</ref>
* [[BK channel|BK<sub>Ca</sub>]]-specific
** [[GAL-021]]<ref>{{cite journal | last1 = McLeod | first1 = JF | last2 = Leempoels | first2 = JM | last3 = Peng | first3 = SX | last4 = Dax | first4 = SL | last5 = Myers | first5 = LJ | last6 = Golder | first6 = FJ | title = GAL-021, a new intravenous BK<sub>Ca</sub>-channel blocker, is well tolerated and stimulates ventilation in healthy volunteers | journal = British Journal of Anaesthesia | date = November 2014 | volume = 113 | issue = 5 | pages = 875–83 | doi = 10.1093/bja/aeu182 | pmid = 24989775 | doi-access = free }}</ref>
** [[Alcohol (drug)|Ethanol (alcohol)]]<ref name="pmid27238266">{{cite journal | vauthors = Dopico AM, Bukiya AN, Kuntamallappanavar G, Liu J | title = Modulation of BK Channels by Ethanol | journal = International Review of Neurobiology | volume = 128 | pages = 239–79 | year = 2016 | pmid = 27238266 | pmc = 5257281 | doi = 10.1016/bs.irn.2016.03.019 | isbn = 9780128036198 }}</ref>
== Inwardly rectifying channel blockers ==
Examples of [[Inward-rectifier potassium ion channel|inwardly rectifying]] channel blockers include:
===[[ROMK]] (K<sub>ir</sub>1.1) ===
Nonselective: [[Barium|Ba<sup>2+</sup>]],<ref name=":1">{{cite book|url=https://archive.org/details/Handbook_of_Inorganic_Chemistry_Patnaik|title=Handbook of inorganic chemicals|publisher=McGraw-Hill|author=Patnaik, Pradyot|date=2003|isbn=978-0-07-049439-8|pages=[https://archive.org/details/Handbook_of_Inorganic_Chemistry_Patnaik/page/n115 77]–78}}</ref> [[Caesium|Cs<sup>+</sup>]]<ref>{{Cite journal|last1=Sackin|first1=H|last2=Syn|first2=S|last3=Palmer|first3=L G|last4=Choe|first4=H|last5=Walters|first5=D E|date=Feb 2001|title=Regulation of ROMK by extracellular cations.|journal=Biophysical Journal|volume=80|issue=2|pages=683–697|issn=0006-3495|pmc=1301267|pmid=11159436|doi=10.1016/S0006-3495(01)76048-1|bibcode=2001BpJ....80..683S}}</ref>
===[[G protein-coupled inwardly-rectifying potassium channel|GPCR regulated]] (K<sub>ir</sub>3.x) ===
*[[GPCR]] antagonists{{Example needed|date=May 2019}}
*[[Ifenprodil]]<ref name="pmid161237692">{{cite journal|vauthors=Kobayashi T, Washiyama K, Ikeda K|date=March 2006|title=Inhibition of G protein-activated inwardly rectifying K+ channels by ifenprodil|journal=Neuropsychopharmacology|volume=31|issue=3|pages=516–24|doi=10.1038/sj.npp.1300844|pmid=16123769|s2cid=10093765|doi-access=free}}</ref>
*[[Caramiphen]] {{Citation needed|date=May 2019}}
*[[Cloperastine]]<ref name="SoedaFujieda2016">{{cite journal|last1=Soeda|first1=Fumio|last2=Fujieda|first2=Yoshiko|last3=Kinoshita|first3=Mizue|last4=Shirasaki|first4=Tetsuya|last5=Takahama|first5=Kazuo|year=2016|title=Centrally acting non-narcotic antitussives prevent hyperactivity in mice: Involvement of GIRK channels|journal=Pharmacology Biochemistry and Behavior|volume=144|pages=26–32|doi=10.1016/j.pbb.2016.02.006|pmid=26892760|s2cid=30118634|issn=0091-3057}}</ref><ref name="YAMAMOTOSOEDA2011">{{cite journal|last1=YAMAMOTO|first1=Gen|last2=SOEDA|first2=Fumio|last3=SHIRASAKI|first3=Tetsuya|last4=TAKAHAMA|first4=Kazuo|year=2011|title=Is the GIRK Channel a Possible Target in the Development of a Novel Therapeutic Drug of Urinary Disturbance?|journal=Yakugaku Zasshi|volume=131|issue=4|pages=523–532|doi=10.1248/yakushi.131.523|pmid=21467791|issn=0031-6903|doi-access=free}}</ref><ref name="KAWAURAHONDA2010">{{cite journal|last1=KAWAURA|first1=Kazuaki|last2=HONDA|first2=Sokichi|last3=SOEDA|first3=Fumio|last4=SHIRASAKI|first4=Tetsuya|last5=TAKAHAMA|first5=Kazuo|year=2010|title=A Novel Antidepressant-like Action of Drugs Possessing GIRK Channel Blocking Action in Rats|journal=Yakugaku Zasshi|volume=130|issue=5|pages=699–705|doi=10.1248/yakushi.130.699|pmid=20460867|issn=0031-6903|doi-access=free}}</ref>
*[[Clozapine]] {{Citation needed|date=May 2019}}
*[[Dextromethorphan]] {{Citation needed|date=May 2019}}
*[[Ethosuximide]] {{Citation needed|date=May 2019}}
*[[Tertiapin]]<ref name="Jinnovel">{{cite journal|last1=Jin|first1=W|last2=Lu|first2=Z|year=1998|title=A novel high affinity inhibitor for inward-rectifier K+ channels|journal=Biochemistry|volume=37|issue=38|pages=13291–13299|doi=10.1021/bi981178p|pmid=9748337}}</ref><ref name="Rang60" />
*[[Tipepidine]]<ref name="KawauraOgata2009">{{cite journal|last1=Kawaura|first1=Kazuaki|last2=Ogata|first2=Yukino|last3=Inoue|first3=Masako|last4=Honda|first4=Sokichi|last5=Soeda|first5=Fumio|last6=Shirasaki|first6=Tetsuya|last7=Takahama|first7=Kazuo|year=2009|title=The centrally acting non-narcotic antitussive tipepidine produces antidepressant-like effect in the forced swimming test in rats|journal=Behavioural Brain Research|volume=205|issue=1|pages=315–318|doi=10.1016/j.bbr.2009.07.004|pmid=19616036|s2cid=29236491|issn=0166-4328|url=https://kumadai.repo.nii.ac.jp/record/24712/files/BBR_205_1_315-318.pdf}}</ref>
*[[CGP-7930]]<ref>{{cite journal | vauthors = Hannan SB, Penzinger R, Mikute G, Smart TG|  title = CGP7930 - An allosteric modulator of GABABRs, GABAARs and inwardly-rectifying potassium channels | journal = Neuropharmacology | volume = 109644 | date = July 2023 | pmid = 37422181 | doi = 10.1016/j.neuropharm.2023.109644| doi-access = free }}</ref>
*[[Barium|Ba<sup>2+</sup>]]<ref name=":1" />
===[[ATP-sensitive K+ channels|ATP-sensitive]] (K<sub>ir</sub>6.x) ===
{{Col-begin}}
{{Col-break}}
*[[Meglitinide]]s (Non-[[Sulfonylurea]]s)
**[[Mitiglinide]]
**[[Nateglinide]]
**[[Repaglinide]]
*[[Sulfonylurea]]s
**[[Acetohexamide]] {{Citation needed|date=May 2019}}
**[[Carbutamide]] {{Citation needed|date=May 2019}}
**[[Chlorpropamide]] {{Citation needed|date=May 2019}}
**[[Glycyclamide]]
**[[Metahexamide]]{{Col-break}}
*[[Sulfonylurea]]s (continued)
**[[Tolazamide]]
**[[Tolbutamide]]
**[[Glibornuride]] {{Citation needed|date=May 2019}}
**[[Glisoxepide]]
**[[Glyclopyramide]]
**[[Gliclazide]]<ref>{{cite journal|last1=Lawrence|first1=C. L.|last2=Proks|first2=P.|last3=Rodrigo|first3=G. C.|last4=Jones|first4=P.|last5=Hayabuchi|first5=Y.|last6=Standen|first6=N. B.|last7=Ashcroft|first7=F. M.|year=2001|title=Gliclazide produces high-affinity block of K ATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells|journal=Diabetologia|volume=44|issue=8|pages=1019–25|doi=10.1007/s001250100595|pmid=11484080|s2cid=12635381|doi-access=free}}</ref>
**[[Glibenclamide|Glibenclamide (glyburide)]]<ref name="pmid17015627">{{cite journal|vauthors=Serrano-Martín X, Payares G, Mendoza-León A|date=December 2006|title=Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis|journal=Antimicrob. Agents Chemother.|volume=50|issue=12|pages=4214–6|doi=10.1128/AAC.00617-06|pmc=1693980|pmid=17015627}}</ref><ref name="Rang60" />
**[[Glipizide]] {{Citation needed|date=May 2019}}
**[[Glimepiride]] {{Citation needed|date=May 2019}}
**[[Glicaramide]] {{Citation needed|date=May 2019}}{{Col-end}}
== Tandem pore domain channel blockers ==
Examples of [[Tandem pore domain potassium channel|tandem pore domain]] channel blockers include:
*[[Bupivacaine]]<ref name="pmid10201682">{{cite journal|vauthors=Kindler CH, Yost CS, Gray AT|date=Apr 1999|title=Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem|journal=Anesthesiology|volume=90|issue=4|pages=1092–102|doi=10.1097/00000542-199904000-00024|pmid=10201682|doi-access=free}}</ref><ref name="pmid11249964">{{cite journal|vauthors=Meadows HJ, Randall AD|date=Mar 2001|title=Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel|journal=Neuropharmacology|volume=40|issue=4|pages=551–9|doi=10.1016/S0028-3908(00)00189-1|pmid=11249964|s2cid=20181576}}</ref><ref name="pmid12660311">{{cite journal|vauthors=Kindler CH, Paul M, Zou H, Liu C, Winegar BD, Gray AT, Yost CS|date=Jul 2003|title=Amide local anesthetics potently inhibit the human tandem pore domain background K+ channel TASK-2 (KCNK5)|journal=The Journal of Pharmacology and Experimental Therapeutics|volume=306|issue=1|pages=84–92|doi=10.1124/jpet.103.049809|pmid=12660311|s2cid=1621972}}</ref><ref name="pmid12760993">{{cite journal|vauthors=Punke MA, Licher T, Pongs O, Friederich P|date=Jun 2003|title=Inhibition of human TREK-1 channels by bupivacaine|journal=Anesthesia and Analgesia|volume=96|issue=6|pages=1665–73|doi=10.1213/01.ANE.0000062524.90936.1F|pmid=12760993|s2cid=39630495|doi-access=free}}</ref>
*[[Quinidine]]<ref name="pmid11249964" /><ref name="pmid8605869">{{cite journal|vauthors=Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J|date=Mar 1996|title=TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure|journal=The EMBO Journal|volume=15|issue=5|pages=1004–11|doi=10.1002/j.1460-2075.1996.tb00437.x|pmc=449995|pmid=8605869}}</ref><ref name="pmid9312005">{{cite journal|vauthors=Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M|date=Sep 1997|title=TASK, a human background K+ channel to sense external pH variations near physiological pH|journal=The EMBO Journal|volume=16|issue=17|pages=5464–71|doi=10.1093/emboj/16.17.5464|pmc=1170177|pmid=9312005}}</ref><ref name="pmid9812978">{{cite journal|vauthors=Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, Lazdunski M|date=Nov 1998|title=Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney|journal=The Journal of Biological Chemistry|volume=273|issue=47|pages=30863–9|doi=10.1074/jbc.273.47.30863|pmid=9812978|s2cid=20414039|doi-access=free}}</ref><ref name="pmid10784345">{{cite journal|vauthors=Meadows HJ, Benham CD, Cairns W, Gloger I, Jennings C, Medhurst AD, Murdock P, Chapman CG|date=Apr 2000|title=Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel|journal=Pflügers Archiv|volume=439|issue=6|pages=714–22|doi=10.1007/s004240050997|pmid=10784345}}</ref>
*[[Fluoxetine]]<ref name = pmid15685212>{{cite journal|author=Kennard|year=2005|title=Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine.|journal=British Journal of Pharmacology|volume=144|issue=6|pages=821–9|pmid = 15685212|pmc=1576064|doi=10.1038/sj.bjp.0706068}}</ref>
*[[Seproxetine]] (Norfluoxetine)<ref name = pmid15685212/>
* [[12-O-Tetradecanoylphorbol-13-acetate|12-''O''-tetradecanoylphorbol-13-acetate]] (TPA) (phorbol 12-myristate 13-acetate).<ref>{{cite web|url=https://www.uniprot.org/uniprot/Q9NPC2|title=UniProtKB - Q9NPC2 (KCNK9_HUMAN)|access-date=2019-05-29|publisher=[[Uniprot]]}}</ref>
== Voltage-gated channel blockers ==
{{more citations needed section|date=May 2019}}
Examples of [[Voltage-gated potassium channel|voltage-gated]] channel blockers include:{{Col-begin}}
{{Col-break}}
*Some types of [[dendrotoxin]]s<ref name="Rang60" />
*[[3,4-Diaminopyridine|3,4-Diaminopyridine (amifampridine)]]<ref name="kirsch narahashi 1978">{{cite journal|journal=Biophys J|title=3,4-diaminopyridine. A potent new potassium channel blocker|date=June 1978|volume=22|issue=3|pages=507–12|vauthors=Kirsch GE, Narahashi T|pmc=1473482|pmid=667299|doi=10.1016/s0006-3495(78)85503-9|bibcode=1978BpJ....22..507K}}</ref>
*[[4-Aminopyridine|4-Aminopyridine (fampridine/dalfampridine)]]<ref>{{cite journal |vauthors=Judge S, Bever C |title=Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment |journal=Pharmacol. Ther. |volume=111 |issue=1 |pages=224–59 |year=2006 |pmid=16472864 |doi=10.1016/j.pharmthera.2005.10.006}}</ref>
*[[Adekalant]]{{citation needed|date=May 2019}}
*[[Almokalant]]{{citation needed|date=May 2019}}
*[[Amiodarone]]<ref group = NB>Amiodarone also blocks [[CACNA2D2]]-containing [[voltage gated calcium channel]]s</ref><ref>{{cite web |url=https://www.drugbank.ca/drugs/DB01118|publisher=Drugbank|title=Amiodarone|access-date=2019-05-28}}</ref><ref name=PMID18505444>{{Cite journal|last1=Wang|first1=Shao-Ping|last2=Wang|first2=Jian-An|last3=Luo|first3=Rong-Hua|last4=Cui|first4=Wen-Yu|last5=Wang|first5=Hai|date=September 2008|title=Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation|journal=Clinical and Experimental Pharmacology & Physiology|volume=35|issue=9|pages=1077–1084|doi=10.1111/j.1440-1681.2008.04964.x|issn=1440-1681|pmid=18505444|s2cid=205457755}}</ref>
*[[Azimilide]]{{citation needed|date=May 2019}}
*[[Bretylium]]<ref name="pmid1667290">{{cite journal |last1=Tiku |first1=Patience E. |last2=Nowell |first2=Peter T. |title=Selective inhibition of K<sup>+</sup>-stimulation of Na,K-ATPase by bretylium |journal=British Journal of Pharmacology |volume=104 |issue=4 |pages=895–900 |year=1991 |pmid=1667290 |pmc=1908819 |doi=10.1111/j.1476-5381.1991.tb12523.x }}</ref>
*[[Bunaftine]]
*[[Charybdotoxin]]{{Col-break}}
*[[Clamikalant]]
*[[Conotoxin]]s, such as κ-conotoxin,<ref name="pmid94170432">{{cite journal|vauthors=Shon KJ, Stocker M, Terlau H, Stühmer W, Jacobsen R, Walker C, Grilley M, Watkins M, Hillyard DR, Gray WR, Olivera BM|year=1998|title=kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel|journal=J. Biol. Chem.|volume=273|issue=1|pages=33–38|doi=10.1074/jbc.273.1.33|pmid=9417043|s2cid=26009966|doi-access=free}}</ref>
*[[Dalazatide]]<!--Kv1.3-selective-->
*[[Dofetilide]]<ref group = NB>works by selectively blocking the rapid component of the [[delayed rectifier outward potassium current]] (I<sub>Kr</sub>)</ref><ref name="pmid17187453">{{cite journal|author1=Roukoz H|author2=Saliba W|date=January 2007|title=Dofetilide: a new class III antiarrhythmic agent|journal=Expert Rev Cardiovasc Ther|volume=5|issue=1|pages=9–19|doi=10.1586/14779072.5.1.9|pmid=17187453|s2cid=11255636}}</ref>
*[[Dronedarone]],<ref name="Guillemare">Guillemare E, Marion A, Nisato D, Gautier P, “Inhibitory effects of dronedarone on muscarinic K+ current in guinea pig atrial cells,” in Journal of Cardiovascular Pharmacology, 2000 7</ref>
*[[E-4031]]<ref group = NB>blocks [[potassium channel]]s of the [[HERG|hERG-type]]</ref><ref>Kim I, Boyle KM, Carrol JL (2005) Postnatal development of E-4031-sensitive potassium current in rat carotid [[chemoreceptor]] cells. ''J Appl Physiol'' '''98'''(4):1469-1477,</ref>
* [[Guangxitoxin]]<ref group = NB>Primarily inhibits outward [[voltage-gated]] [[KCNB1|K<sub>v</sub>2.1]] [[potassium channel]] [[Electric current|currents]].</ref><ref name=HerringtonJ2006>{{cite journal | vauthors = Herrington J, Zhou YP, Bugianesi RM, Dulski PM, Feng Y, Warren VA, Smith MM, Kohler MG, Garsky VM, Sanchez M, Wagner M, Raphaelli K, Banerjee P, Ahaghotu C, Wunderler D, Priest BT, Mehl JT, Garcia ML, McManus OB, Kaczorowski GJ, Slaughter RS | title = Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion | journal = Diabetes | volume = 55 | issue = 4 | pages = 1034–42 | date = April 2006 | pmid = 16567526 | doi = 10.2337/diabetes.55.04.06.db05-0788 | doi-access = free }}</ref><ref name=HerringtonJ2007>{{cite journal | vauthors = Herrington J | title = Gating modifier peptides as probes of pancreatic beta-cell physiology | journal = Toxicon | volume = 49 | issue = 2 | pages = 231–8 | date = February 2007 | pmid = 17101164 | doi = 10.1016/j.toxicon.2006.09.012 }}</ref>
*[[Hanatoxin]]
*[[HgeTx1]]
*[[HsTx1]]<ref group = NB> a very potent inhibitor of the rat [[KCNA3|Kv1.3]] [[voltage-gated potassium channel]]</ref><ref name="lebrun">{{cite journal|last1=Lebrun|first1=Bruno|date=1997|title=A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom|journal=Biochemical Journal|volume=328|issue=Pt 1|pages=321–327|pmc=1218924|pmid=9359871|doi=10.1042/bj3280321}}</ref>
{{Col-break}}
*[[Ibutilide]],<ref>{{cite journal|last1=Murray|first1=K. T.|date=10 February 1998|title=Ibutilide|journal=Circulation|volume=97|issue=5|pages=493–497|doi=10.1161/01.CIR.97.5.493|pmid=9490245|doi-access=free}}</ref>
*[[Inakalant]]
*[[Kaliotoxin]]
*[[Linopirdine]]
*[[Lolitrem B]]
*[[Maurotoxin]]
*[[Nifekalant]]
*[[Notoxin]]
*[[Parabutoxin]]<ref name="a subfamily">{{cite journal|last=Huys, I|author2=Olamendi-Portugal, T |author3=Garci-Goméz, BI |author4= Vandenberghe, I |title=A subfamily of acidic alpha-K(+) toxins|journal=J Biol Chem|year=2004|volume=279|issue=4|pages=2781–9|doi=10.1074/jbc.M311029200|pmid=14561751|doi-access=free}}</ref>
*[[Paxilline]]
*[[Pinokalant]]
{{Col-break}}
*[[Quinidine]]
*[[ShK-186]]<!--Kv1.3-selective-->
*[[Sotalol]]
*[[Tedisamil]]
*[[Terikalant]]
*[[Tetraethylammonium]]<ref>B. Hille (1967). "The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ions." ''J. Gen. Physiol.'' '''50''' 1287-1302.</ref><ref name = Arm>C. M. Armstrong (1971). "Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons." ''J. Gen. Physiol.'' '''58''' 413-437.</ref>
* [[Verapamil]]<ref name=PMID18505444 />
*[[Vernakalant]]{{Col-break}}
{{Col-end}}
=== [[hERG]] (KCNH2, K<sub>v</sub>11.1)-specific ===
{{Col-begin}}
{{Col-break}}
*[[Ajmaline]]
*[[Amiodarone]]
*[[AmmTX3]]
*[[Astemizole]]
*[[Azaspiracid]]
*[[AZD1305]]
*[[Azimilide]]
*[[Bedaquiline]]
*[[BeKm-1 toxin|BeKm-1]]{{Col-break}}
*[[BmTx3]]
*[[BRL-32872]]
*[[Chlorpromazine]]
*[[Cisapride]]
*[[Clarithromycin]]
*[[Darifenacin]]
*[[Dextropropoxyphene]]
*[[Diallyl trisulfide]]
*[[Domperidone]]{{Col-break}}
*[[E-4031]]
*[[Ergtoxin]]s
*[[Erythromycin]]
*[[Gigactonine]]
*[[Haloperidol]]
*[[Ketoconazole]]
*[[Norpropoxyphene]]
*[[Orphenadrine]]
*[[Pimozide]]{{Col-break}}
*[[PNU-282,987]]
*[[Promethazine]]
*[[Quinidine]]
*[[Ranolazine]]
*[[Roxithromycin]]
*[[Sertindole]]
*[[Solifenacin]]
*[[Tamulotoxin]]
*[[Terodiline]]
*[[Terfenadine]]{{Col-break}}
*[[Thioridazine]]
*[[Tolterodine]]
*[[Vanoxerine]]
*[[Vernakalant]]
{{Col-end}}
=== [[KCNQ_channels|KCNQ (K<sub>v</sub>7)]]-specific ===
* [[Linopirdine]]
*[[XE-991]]
*[[Ssm spooky toxin|Spooky toxin (SsTx)]]
==See also==
* [[Potassium channel]]
* [[Potassium channel opener]]
==Notes==
{{reflist|group=NB}}
==References==
{{Reflist}}
{{Channel blockers}}
{{Antiarrhythmic agents}}
[[Category:Potassium channel blockers| ]]