. 2021 Oct 27;10(11):2914. doi: 10.3390/cells10112914

Table 3.

Pharmacological profile of K_2P-channels.

K_2P Channel	Drug/Compound	Effect (Organism)	EC₅₀ /IC₅₀ (Organism)	Citation
K_2P1.1 (TWIK-1)	Quinine	Inhibition (XO)	50 µM (XO)	[20]
	Quinidine	Inhibition (XO)	95 µM (XO)	[20]
	Barium	Inhibition (XO)	100 µM (XO)	[20]
	Charybdotoxin	< 10% inhibition at 3 nM (XO)	n.m.	[20]
	Dendrotoxin	< 10% inhibition at 100 nM (XO)	n.m.	[20]
	Apamin	< 10% inhibition at 300 nM (XO)	n.m.	[20]
	Clofilium	< 10% inhibition at 30 µM (XO)	n.m.	[20]
	Glibenclamid	< 10% inhibition at 30 µM (XO)	n.m.	[20]
	Cromakalim	No effect at 100 µM (XO)	n.m.	[20]
	Tedisamil	30% inhibition at 100 µM (XO)	n.m.	[20]
	Dronedarone	No significant effect at 100 µM (XO)	n.m.	[82]
	Amiodarone	< 10% inhibition at 100 µM (XO)	n.m.	[20]
	Pinacidil	No effect at 100 µM (XO)	n.m.	[20]
	Vernakalant	No significant effect at 100 µM (XO)	n.m.	[83]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Genistein	No significant effect at 100 µM (XO)	n.m.	[85]
	4-AP	< 10% inhibition at 1 mM (XO)	n.m.	[20]
	TEA	30% inhibition at 10 mM (XO)	n.m.	[20]
K_2P2.1 (TREK-1)	GI-530159	High affinity K_2P2.1 activator (MC)	890 nM (MC)	[86]
	Copper	Activation (MC)	3 µM (MC)	[87]
	Ostruthin	Activator (MC)	5.3 µM (MC)	[88]
	BL-1249	High affinity TREK-1/2 activator (XO)	5.5 µM (XO)	[89]
	ML402	High affinity TREK-1/2 activator (XO)	13.7 µM (XO)	[90]
	ML335	High affinity TREK-1/2 activator (XO)	14.3 µM (XO)	[90]
	ML67-33	High affinity TREK-1/2 activator (XO)	36.3 µM (XO); 9.7 µM (MC)	[91]
	Pranlukast	66.4% activation at 3 µM (MC)	n.m.	[92]
	DCPIB	~3-fold activation at 10 µM (MC)	n.m.	[93]
	Morphine	~2-fold activation at 10 µM (MC)	n.m.	[94]
	Flufenamic acid	~4-fold activation at 100 µM (MC)	n.m.	[95]
	Niflumic acid	~2.5-fold activation at 100 µM (MC)	n.m.	[95]
	Mefenamic acid	~2-fold activation at 100 µM (MC)	n.m.	[95]
	Carbamazepine	42% activation at 100 µM (MC)	n.m.	[96]
	Valproate	28% activation at 100 µM (MC)	n.m.	[96]
	Gabapentin	25% activation at 100 µM (MC)	n.m.	[96]
	Diethyl ether	~1.75-fold activation at 600 µM (MC)	n.m.	[97]
	Chloroform	~3.5-fold activation at 800 µM (MC)	n.m.	[97]
	Lithium	31% activation at 1 mM (MC)	n.m.	[96]
	Rubidium	27% activation at 1 mM (MC)	n.m.	[96]
	Halothane	~1.4-fold activation at 1 mM (MC)	n.m.	[97]
	Isoflurane	~1.5-fold activation at 2 mM (MC)	n.m.	[97]
	Cyclopropane	~30% activation at 10% (MC)	n.m.	[98]
	Xenon	~30% activation at 80% (MC)	n.m.	[98]
	Nitrous oxide	~30% activation at 80% (MC)	n.m.	[98]
	Spadin	High affinity K_2P2.1 inhibitor (MC)	40 nM (MC)	[99]
	Amlodipin	Inhibition (MC)	430 nM (MC)	[100]
	Nigludipine	Inhibition (MC)	750 nM (MC)	[100]
	Pimozide	Inhibition (MC)	1.8 µM (MC)	[101]
	Fluphenthixol	Inhibition (MC)	2.0 µM (MC)	[101]
	Chlorpromazine	Inhibition (MC)	2.7 µM (MC)	[96,101]
	Sipatrigine	73.3% inhibition at 10 µM (MC)	4 µM	[59]
	Fluphenazine	Inhibition (MC)	4.7 µM (MC)	[101]
	Haloperidol	Inhibition (MC)	5.5 µM (MC)	[101]
	Norfluoxetine	Inhibition (MC)	9 µM (MC)	[102]
	Vernakalant	Inhibition (MC)	13.3 µM (MC)	[84]
	Loxapine	Inhibition (MC)	19.7 µM (MC)	[101]
	Fluoxetine	Inhibition (MC)	19–37.9 µM (MC)	[96,102]
	Carvedilol	Inhibition (XO, MC)	20.3 μM (XO); 1.6 μM (MC)	[42]
	A1899 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	23.8 µM (XO)	[103]
	Dronedarone	Inhibition (XO, MC)	26.7 μM (XO); 6.1 μM (MC)	[82]
	Propafenone	Inhibition (XO, MC)	51.0 μM (XO); 7.9 μM (MC)	[104]
	Levobupivacaine	Inhibition (MC)	126 µM (MC)	[105]
	Diltiazem	Inhibitor (MC)	180 µM (MC)	[95]
	Lidocaine	Inhibition (MC)	207 μM (MC)	[106]
	Bupivacaine	Inhibition (MC)	370 µM (MC)	[107]
	Caffeine	Inhibition (MC)	377 µM (MC)	[108]
	Ropivacaine	Inhibition (MC)	402 µM (MC)	[105]
	Theophylline	Inhibition (MC)	486 µM (MC)	[108]
	Zinc	Inhibition (MC)	659 µM (MC)	[87]
	Mexiletine	Inhibition (XO, MC)	1.3 mM (XO); 182 μM (MC);	[104]
	Tetramethyl-ammonium	63% inhibition (MC)	n.m.	[24]
	Lamotrigine	~10% inhibition at 10 µM (MC)	n.m.	[59]
	Metoprolol	~20% inhibition at 100 µM (XO)	n.m.	[42]
	Propranolol	~30% inhibition at 100 µM (XO)	n.m.	[42]
	Citalopram	59% inhibition at 100 µM (MC)	n.m.	[96]
	Barium	50% inhibition at 300 µM (XO)	n.m.	[24]
	Ranolazine	7.35% inhibition at 300 µM (XO)	n.m.	[109]
	Clozapine	Inhibition (MC)	n.m.	[101]
	Sulpiride	No significant effect at 10 µM (MC)	n.m.	[101]
	Tiapride	No significant effect at 10 µM (MC)	n.m.	[101]
	Glibenclamide	No significant effect at 10 µM (XO)	n.m.	[24]
	Cesium	No significant effect at 100 µM (XO)	n.m.	[24]
	Gadolineum	No significant effect at 100 µM (XO)	n.m.	[24]
TEA	No significant effect at 100 µM (XO)	n.m.	[24]
Quinine	No significant effect at 100 µM (XO)	n.m.	[24]
Quinidine	No significant effect at 100 µM (XO)	n.m.	[24]
Tedisamil	No significant effect at 100 µM (XO)	n.m.	[24]
Genistein	No significant effect at 100 µM (XO)	n.m.	[85]
Flecainide	No significant effect at 100 µM (XO, MC)	n.m.	[84]
Amiodarone	No significant effect (XO)	n.m.	[110]
Sotalol	No significant effect (XO)	n.m.	[82]
Digoxin	No significant effect (XO)	n.m.	[111]
Digitoxin	No significant effect (XO)	n.m.	[111]
A293	No significant effect (XO)	n.m.	[10]
Ajmaline	No significant effect (MC)	n.m.	[104]
GsMTx4	No significant effect (MC)	n.m.	[112]
Magnesium	No significant effect (XO)	n.m.	[24]
K_2P3.1 (TASK-1)	Halothane	Activation (XO, MC)	300–1000 µM (XO)	[97,113,114]
	Sevoflurane	~40% activation at 1 mM	n.m.	[114]
	Isoflurane	~15% activation at 1 mM (XO) ~20% activation at 2 mM (MC)	n.m.	[97,113]
	BAY2341237	High affinity K_2P3.1 inhibitor	7.6 nM (XO)	[115]
	BAY1000493	High affinity K_2P3.1 inhibitor	9.5 nM (XO)	[115]
	ML365	High affinity K_2P3.1 inhibitor	16 nM (MC)	[116]
	A1899 (S20951)	High affinity K_2P3.1 inhibitor	35 nM (XO); 7 nM (MC)	[103,115]
	S9947 (K_V1.5 blocker)	Inhibition (XO)	200 nM (XO)	[103,117]
	A293 (AVE1231)	High affinity K_2P3.1 inhibitor	222 nM (XO)	[10,15]
	PK-THPP	Inhibition (XO)	243 nM	[118]
	MSD-D (K_V1.5 blocker)	Inhibition (XO)	350 nM (XO)	[117]
	Amiodarone	Inhibition (XO)	400 nM (XO)	[82,110]
	Doxapram	Inhibition (XO, MC)	410 nM (XO)	[119]
	AVE0118 (K_V1.5 blocker)	Inhibition (XO)	600 nM (XO)	[117]
	Methanandamide	Inhibition (XO)	700 nM (MC)	[120]
	Digoxin	Inhibition (XO)	900 nM (XO)	[111]
	ICAGEN-4 (K_V1.5 blocker)	Inhibition (XO)	1.05 µM (XO)	[117]
	ML308 (High affinity K_2P9.1 inhibitor)	Inhibition (MC)	3.2 µM (MC)	[121]
	Carvedilol	Inhibition (XO, MC)	3.8 µM (XO); 0.83 µM (MC)	[42]
	Digitoxin	Inhibition (XO)	7.4 µM (XO)	[111]
	Genistein	81.1% inhibition at 100 µM (XO)	12.3 µM (MC)	[85]
	Dronedarone	Inhibition (XO, MC)	18.7 µM (XO); 5.2 µM (MC)	[82]
	Propafenone	Inhibition (XO, MC)	18.1 μM (XO); 5.1 μM (MC);	[104]
	Etidocaine	Inhibition (XO)	39 µM (XO)	[122]
	Ostruthin	Inhibition (MC)	41 µM (MC)	[88]
	R-Ropivacaine	Inhibition (XO)	51 µM (XO)	[122]
	S-Ropivacaine	Inhibition (XO)	53 µM (XO)	[122]
	Bupivacaine	Inhibition (XO)	68 µM (XO)	[123]
	Etomidate	Inhibition (XO)	119 µM (XO)	[113]
	Zinc	Inhibition (XO)	175 µM (XO)	[123]
	Ranolazine	Inhibition (XO, MC)	198.4 µM (XO); 30.6 µM (MC)	[109]
	Lidocain	Inhibition (XO)	222 µM (XO)	[122]
	Mexiletine	Inhibition (XO, MC)	405 µM (XO); 97.3 μM (MC)	[104]
	Tetracaine	Inhibition (XO)	668 µM	[122]
	Mepivacaine	Inhibition (XO)	709 µM (XO)	[122]
	Agitoxin	< 15%inhibition at 1 nM (XO)	n.m.	[123]
	Margatoxin	< 15%inhibition at 10 nM (XO)	n.m.	[123]
	Dendrotoxin	< 15%inhibition at 100 nM (XO)	n.m.	[123]
	Charybdotoxin	< 15%inhibition at 200 nM (XO)	n.m.	[123]
	Anandamide	~90% inhibition at 3 µM (MC)	n.m.	[120]
	CP55940 (CB1/CB2agonist)	~50% inhibition at 10 µM (MC)	n.m.	[120]
	Sipatrigine	37%inhibition at 10 µM (MC)	n.m.	[59]
	Glibenclamid	< 15%inhibition at 30 µM (XO)	n.m.	[123]
	Propranolol	~60% inhibition at 100 µM (XO)	n.m.	[42]
	Cesium	31% inhibition at 100 µM (XO)	n.m.	[45]
	Quinidine	< 20–71 % inhibition at 100 µM (XO)	n.m.	[45,123]
	Quinine	< 20 % inhibition at 100 µM (XO)	n.m.	[45]
	Quinacrine	< 20% inhibition at 100 µM (XO)	n.m.	[45]
	Barium	~19% inhibition at 100 µM (XO)	n.m.	[45]
	Daidzein	18.2% inhibition at 100 µM (XO)	n.m.	[85]
	Cromakalim	< 15%inhibition at 100 µM (XO)	n.m.	[123]
	Metoprolol	~10% inhibition at 100 µM (XO)	n.m.	[42]
	Phenytoin	~50% inhibition at 200 µM (XO)	n.m.	[123]
	Diethyl ether	~45 % at 600 µM (MC)	n.m.	[97]
	Magnesium	~14% inhibition at 10 mM (XO)	n.m.	[123]
	4-AP	<15%inhibition at 10 mM (XO)	n.m.	[45,123]
	Flecainide	No significant effect at 100 µM (XO, MC)	n.m.	[84]
	Ouabain	No significant effect at 100 µM (XO)	n.m.	[111]
	Vernakalant	No significant effect at 100 µM (XO, MC)	n.m.	[84]
	Sotalol	No significant effect at 100 µM (XO)	n.m.	[82]
	Genistin	No significant effect at 100 µM (XO)	n.m.	[85]
	Propofol	No significant effect at 200 µM (XO)	n.m.	[113]
	Chloroform	No significant effect at 800 µM (MC)	n.m.	[97]
	TEA	No significant effect at 1 mM (XO)	n.m.	[45]
K_2P4.1 (TRAAK)	Sipatrigine	45%inhibition at 10 µM (MC)	10 µM	[59]
	ML67-33 (High affinity TREK-1/2 activator)	Activation (XO, MC)	27.3 µM (XO); 1.8 µM (MC)	[91]
	BL-1249 (High affinity TREK-1/2 activator)	Activation (XO)	48 µM (XO)	[89]
	A1899 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	>20 µM (XO)	[103]
	Docosahexaenoate	~12-fold activation at 10 µM (MC)	n.m.	[58]
	Eicosapentaenoate	~8-fold activation at 10 µM (MC)	n.m.	[58]
	Arachidonic acid	~5-fold activation at 10 µM (MC)	n.m.	[58]
	Oleate	~1.5-fold activation at 10 µM (MC)	n.m.	[58]
	Linoleate	~1.5-fold activation at 10 µM (MC)	n.m.	[58]
	Riluzole	3.9-fold activation at 100 µM (MC)	n.m.	[58]
	Flufenamic acid	~2-fold activation at 100 µM (MC)	n.m.	[95]
	Niflumic acid	~2-fold activation at 100 µM (MC)	n.m.	[95]
	Mefenamic acid	~1.6-fold activation at 100 µM (MC)	n.m.	[95]
	Lamotrigine	~10% inhibition at 10 µM (MC)	n.m.	[59]
	Vernakalant	17.1% inhibition at 100 µM (XO)	n.m.	[83]
	Barium	56.7% inhibition at 1 mM (XO)	n.m.	[58]
	Charybdotoxin	No significant effect at 20 nM (XO)	n.m.	[58]
	Dendrotoxin	No significant effect at 100 nM (XO)	n.m.	[58]
	Tetrodotoxin	No significant effect at 1 µM (XO)	n.m.	[58]
	Tedisamil	No significant effect at 10 µM (XO)	n.m.	[58]
	Palmitate	No significant effect at 10 µM (MC)	n.m.	[58]
	Stearate	No significant effect at 10 µM (MC)	n.m.	[58]
	Arachidate	No significant effect at 10 µM (MC)	n.m.	[58]
	Fluphenazine	No significant effect at 10 µM (MC)	n.m.	[101]
	Chlorpromazine	No significant effect at 10 µM (MC)	n.m.	[101]
	Haloperidol	No significant effect at 10 µM (MC)	n.m.	[101]
	Fluphenthixol	No significant effect at 10 µM (MC)	n.m.	[101]
	Loxapine	No significant effect at 10 µM (MC)	n.m.	[101]
	Pimozide	No significant effect at 10 µM (MC)	n.m.	[101]
	Clozapine	No significant effect at 10 µM (MC)	n.m.	[101]
	Sulpiride	No significant effect at 10 µM (MC)	n.m.	[101]
	Tiapride	No significant effect at 10 µM (MC)	n.m.	[101]
	Tolbutamide	No significant effect at 100 µM (XO)	n.m.	[58]
	Pinacidil	No significant effect at 100 µM (XO)	n.m.	[58]
	P1060	No significant effect at 100 µM (XO)	n.m.	[58]
	Glibenclamide	No significant effect at 200 µM (XO)	n.m.	[58]
	Cobalt	No significant effect at 500 µM (XO)	n.m.	[58]
	Dronedarone	No significant effect at 100 µM (XO)	n.m.	[82]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Genistein	No significant effect at 100 µM (XO)	n.m.	[85]
	Ranolazine	3.32 % inhibition at 300 µM (XO)	n.m.	[109]
	Diethyl ether	No significant effect at 600 µM (MC)	n.m.	[97]
	Chloroform	No significant effect at 800 µM (MC)	n.m.	[97]
	Halothane	No significant effect at 1 mM (MC)	n.m.	[97]
	Diltiazem	No significant effect at 1 mM (MC)	n.m.	[95]
	TEA	No significant effect at 1 mM (XO)	n.m.	[58]
	4-AP	No significant effect at 1 mM (XO)	n.m.	[58]
	Caesium	No significant effect at 1 mM (XO)	n.m.	[58]
	Isoflurane	No significant effect at 2 mM (MC)	n.m.	[97]
	Digoxin	No significant effect (XO)	n.m.	[111]
	Digitoxin	No significant effect (XO)	n.m.	[111]
K_2P5.1 (TASK-2)	A293 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	8.1 nM (XO)	[10,15]
	A1899 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	12 µM (XO)	[103]
	Quinine	Inhibition (XO)	22.4 µM (XO)	[17]
	Quinidine	65% inhibition at 100 µM (XO)	n.m.	[17]
	Zinc	15.3% inhibition at 100 µM (XO)	n.m.	[17]
	Ranolazine	30.02% inhibition at 300 µM (XO)	n.m.	[17]
	Barium	16.9% inhibition at 1 mM (XO)	n.m.	[17]
	Lidocaine	60.4% inhibition at 10 mM (XO)	n.m.	[17]
	Bupivacaine	80.9% inhibition at 10 mM (XO)	n.m.	[17]
	Arachidonic acid	No significant effect at 10 µM (XO)	n.m.	[17]
	4-AP	No significant effect at 100 µM (XO)	n.m.	[17]
	Dronedarone	No significant effect at 100 µM (XO)	n.m.	[82]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Genistein	No significant effect at 100 µM (XO)	n.m.	[85]
	Vernakalant	No significant effect at 100 µM (XO)	n.m.	[83]
	Digoxin	No significant effect (XO)	n.m.	[111]
	Digitoxin	No significant effect (XO)	n.m.	[111]
	TEA	No significant effect at 1 mM (XO)	n.m.	[17]
	Cesium	No effect at 1 mM (XO)	n.m.	[17]
K_2P6.1 (TWIK-2)	Barium	Inhibition (MC)	~100 µM (MC)	[124]
	Quinidine	73% inhibition at 100 µM (XO)	n.m.	[124]
	Quinine	73% inhibition at 100 µM (XO)	n.m.	[124]
	Genistein	~30% inhibition at 100 µM (XO)	n.m.	[85]
	Dronedarone	10.7% inhibition at 100 µM (XO)	n.m.	[82]
	Chloroform	32% inhibition at 300 µM (XO)	n.m.	[124]
	Halothane	27% inhibition at 750 µM (XO)	n.m.	[124]
	Cesium	92% inhibition of inward current at 10 mM (XO)	n.m.	[124]
	TEA	No significant effect at 5 mM (XO)	n.m.	[124]
	4-AP	No significant effect at 3 mM (XO)	n.m.	[124]
	Glibenclamide	No significant effect at 10 µM (XO)	n.m.	[124]
	Vernakalant	No significant effect at 100 µM (XO)	n.m.	[83]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
K_2P7.1 (TWIK-3)		Non-functional channel
K_2P9.1 (TASK-3)	DCPIB	~3-fold activation at 10 µM (MC)	n.m.	[93]
	Halothane	65.6% activation at 1 mM (XO)	n.m.	[125]
	BAY2341237 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	2.3 nM (XO)	[115]
	BAY1000493 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	15.1 nM (XO)	[115]
	A1899 (High affinity K_2P3.1 inhibitor)	Inhibition (XO, MC)	318 nM (XO); 70 nM (MC)	[103]
	ML308	High affinity K_2P9.1 inhibitor	413 nM (MC)	[121]
	A293 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	950 nM (XO)	[10,15]
	ML365 (High affinity K_2P3.1 inhibitor)	Inhibition (MC)	990 nM (MC)	[116]
	Copper	Inhibition (MC)	2.7 µM (MC)	[87]
	Zinc	Inhibition (MC)	12.7 µM (MC)	[87]
	Mibefradil	Inhibition (MC)	24.6 μM (MC)	[126]
	Doxapram	Inhibition (XO)	37 µM (XO)	[119]
	L-703,606 oxalate	Inhibition (MC)	45.5 μM (MC)	[126]
	Oligomycine A	Inhibition (MC)	47.7 μM (MC)	[126]
	GW2974	Inhibition (MC)	50.1 µM (MC)	[126]
	Loratadine	Inhibition (MC)	63.4 µM (MC)	[126]
	Dihydro-β-erythroidine hydrobromide	Inhibition (MC)	73.8 µM (MC)	[126]
	(±)-Octoclothepin maleate	Inhibition (MC)	73.8 µM (MC)	[126]
	Ruthenium red	Inhibitor (XO)	114 µM	[127]
	Etomidate	Inhibition (XO)	128 µM (XO)	[113]
	Mevastatin	Inhibition (MC)	159 μM (MC)	[126]
	Ostruthin	Inhibition (MC)	227 µM (MC)	[88]
	Barium	11% inhibition at 100 µM (XO)	290 µM (XO)	[64]
	Arachidonic acid	4.81% inhibition at 10 µM (XO)	n.m.	[125]
	Genistein	~60% inhibition at 100 µM (XO)	n.m.	[85]
	Bupivacaine	50.2–56% inhibition at 100 µM (XO, MC)	n.m.	[70,125]
	Alphaxolone	49.2% inhibition at 100 µM (XO)	n.m.	[125]
	Quinidine	42.2% inhibition at 100 µM (XO)	n.m.	[125]
	Quinine	36.9% inhibition at 100 µM (XO)	n.m.	[125]
	Dronedarone	31.7% inhibition at 100 µM (XO)	n.m.	[82]
	Fluoxetine	31%inhibition at 100 µM (MC)	n.m.	[102]
	Ketamine	7.3% inhibition at 100 µM (XO)	n.m.	[125]
	Pentobarbital	4.3% inhibition at 100 µM (XO)	n.m.	[125]
	Glibenclamide	3.6% inhibition at 100 µM (XO)	n.m.	[125]
	Ranolazine	28.28% inhibition at 300 µM (XO)	n.m.	[109]
	TEA	6% inhibition at 1 mM (XO)	n.m.	[125]
	Xenon	No significant effect at 80% (MC)	n.m.	[98]
	Nitrous oxide	No significant effect at 80% (MC)	n.m.	[98]
	Cyclopropane	No significant effect at 10% (MC)	n.m.	[98]
	Propofol	No significant effect at 200 µM (XO)	n.m.	[113]
	Vernakalant	No significant effect at 100 µM (XO)	n.m.	[83]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Digoxin	No significant effect (XO)	n.m.	[111]
	Digitoxin	No significant effect (XO)	n.m.	[111]
	Cesium	8–12% inhibition at 10 mM (XO)	n.m.	[64,125]
K_2P10.1 (TREK-2)	Ostruthin	Activator (MC)	3.7 µM (MC)	[88]
	ML335	High affinity TREK-1/2 activator	5.2 µM (XO)	[90]
	ML402	High affinity TREK-1/2 activator	5.9 µM (XO)	[90]
	Arachidonic acid	Activation (MC)	7.3 µM (MC)	[65]
	BL-1249	High affinity TREK-1/2 activator	8.0 µM (XO)	[89]
	ML67-33	High affinity TREK-1/2 activator	30.2 µM (XO); 1.6 µM (MC)	[91]
	11-deoxyprostaglandin F2α	~5-fold activation at 2 µM (MC)	n.m.	[128]
	Pranlukast	228 % activation at 3 µM (MC)	n.m.	[92]
	Ocosahexaenoicacid	~5-fold activation at 20 µM (MC)	n.m.	[65]
	Linolenic acid	~6-fold activation at 20 µM (MC)	n.m.	[65]
	Eicosapentaenoic acid	~8-fold activation at 20 µM (MC)	n.m.	[65]
	Linoleic acid	~8-fold activation at 20 µM (MC)	n.m.	[65]
	Flufenamic acid	~4-fold activation at 100 µM (MC)	n.m.	[95]
	Niflumic acid	~2.5-fold activation at 100 µM (MC)	n.m.	[95]
	Mefenamic acid	~2-fold activation at 100 µM (MC)	n.m.	[95]
	Ruthenium red	Inhibition (XO)	230 nM (XO)	[127]
	A1899 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	8.4 µM (XO)	[103]
	Carvedilol	Inhibition (XO, MC)	24 µM (XO); 7.6 (MC)	[43]
	Fluoxetine	68% inhibition at 10 µM (MC)	28.7 µM (MC)	[96]
	Diltiazem	Inhibition (MC)	330 µM (MC)	[95]
	Fluphenthixol	~80% inhibition at 10 µM (MC)	n.m.	[101]
	Pimozide	~80% inhibition at 10 µM (MC)	n.m.	[101]
	Fluphenazine	~70% inhibition at 10 µM (MC)	n.m.	[101]
	Clozapine	~50% inhibition at 10 µM (MC)	n.m.	[101]
	Loxapine	~50% inhibition at 10 µM (MC)	n.m.	[101]
	Haloperidol	~50% inhibition at 10 µM (MC)	n.m.	[101]
	Paroxetin	33% inhibition at 20 µM (MC)	n.m.	[96]
	Citalopram	59% inhibition at 100 µM (MC)	n.m.	[96]
	Chlorpromazine	57% inhibition at 100 µM (MC)	n.m.	[96,101]
	Vernakalant	19.8% inhibition at 100 µM (XO)	n.m.	[83]
	Barium	36% inhibition at 2 mM (MC)	n.m.	[65]
	Sulpiride	No significant effect at 10 µM (MC)	n.m.	[101]
	Tiapride	No significant effect at 10 µM (MC)	n.m.	[101]
	Elaidic acid	No significant effect at 20 µM (MC)	n.m.	[65]
	Stearic acid	No significant effect at 100 µM (MC)	n.m.	[65]
	Palmitic acid	No significant effect at 100 µM (MC)	n.m.	[65]
	Gabapentin	No significant effect at 100 µM (MC)	n.m.	[96]
	Valproate	No significant effect at 100 µM (MC)	n.m.	[96]
	Carbamazepine	No significant effect at 100 µM (MC)	n.m.	[96]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Genistein	No significant effect at 100 µM (XO)	n.m.	[85]
	Dronedarone	No significant effect at 100 µM (XO)	n.m.	[82]
	Quinidine	No significant effect at 100 µM (MC)	n.m.	[65]
	Bupivacaine	No significant effect at 100 µM (MC)	n.m.	[65]
	Gadolinium	No significant effect at 100 µM (MC)	n.m.	[65]
	Ranolazine	No significant effect at 300 µM (XO)	n.m.	[109]
	TEA	No significant effect at 1 mM (MC)	n.m.	[65]
	Lidocaine	No significant effect at 1 mM (MC)	n.m.	[65]
	Lithium	No significant effect at 1 mM (MC)	n.m.	[96]
	Rubidium	No significant effect at 1 mM (MC)	n.m.	[96]
	Digitoxin	No significant effect (XO)	n.m.	[111]
	Digoxin	No significant effect (XO)	n.m.	[111]
K_2P12.1	Quinidine	Inhibition (XO)	160 µM (XO)	[8]
	Halothane	~50% inhibition at 5 mM (XO)	n.m.	[8]
	Arachidonic acid	No significant effect at 5 µM (XO)	n.m.	[8]
K_2P13.1 (THIK-1)	Lysophos-phatidylcholine	~20% activation at 10 µM (XO)	n.m.	[66]
	Arachidonic acid	69.6–85% activation at 5–20 µM (XO)	980 nM (XO)	[66,68]
	Dronedarone	14.9% activation at 100 µM (XO)	n.m.	[82]
	Quinidine	10.9% activation at 100 µM (XO)	n.m.	[129]
	Amiodarone	9.3% activation at 100 µM	n.m.	[129]
	Ranolazine	4.98% activation at 300 µM (XO)	n.m.	[109]
	A1899 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	2.2 µM (XO)	[103]
	Mexiletine	74.6% inhibition at 1.5 mM (XO)	356 µM (XO)	[68,129]
	Halothane	56% inhibition at 5 mM (XO)	2.8 mM (XO)	[66]
	Lidocaine	59.2% inhibition at 100 µM (XO)	n.m.	[68]
	Carvedilol	No significant effect at 100 µM (XO)	n.m.	[129]
	Metoprolol	No significant effect at 100 µM (XO)	n.m.	[129]
	Vernakalant	No significant effect at 100 µM (XO)	n.m.	[83]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Verapamil	No significant effect at 100 µM (XO)	n.m.	[129]
	Propafenone	26% inhibition at 100 µM (XO)	n.m.	[129]
	Genistein	~20% inhibition at 100 µM (XO)	n.m.	[85]
	Propranolol	37.6% inhibition at 200 µM (XO)	n.m.	[129]
	Chloroform	No significant effect at 1 mM (XO)	n.m.	[66]
	Barium	88.7% inhibition at 2 mM (XO)	n.m.	[66,68]
	Digoxin	No significant effect (XO)	n.m.	[111]
	Digitoxin	No significant effect (XO)	n.m.	[111]
K_2P15.1 (TASK-5)		Non-functional channel
K_2P16.1 (THIK-1)	Digitoxin	~30% inhibition at 100 µM (XO)	n.m.	[111]
	Ranolazine	23.04% inhibition at 300 µM (XO)	n.m.	[109]
	Halothane	26.8% inhibition at 800 µM (XO)	n.m.	[67]
	Chloroform	21.5% inhibition at 800 µM (XO)	n.m.	[67]
	Barium	51.4% inhibition at 1 mM (XO)	n.m.	[67]
	Quinine	45.1% inhibition at 1 mM (XO)	n.m.	[67]
	Quinidine	36.8% inhibition at 1 mM (XO)	n.m.	[67]
	TEA	14.9% inhibition at 1 mM (XO)	n.m.	[67]
	Arachidonic acid	No significant effect at 20 µM (XO)	n.m.	[67]
	4-AP	No significant effect at 100 µM (XO)	n.m.	[67]
	Vernakalant	No significant effect at 100 µM (XO)	n.m.	[83]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Genistein	No significant effect at 100 µM (XO)	n.m.	[85]
	Dronedarone	No significant effect at 100 µM (XO)	n.m.	[82]
	Isoflurane	No significant effect at 800 µM (XO)	n.m.	[67]
	Cesium	No significant effect at 1 mM (XO)	n.m.	[67]
	Digoxin	No significant effect (XO)	n.m.	[111]
K_2P17.1 (THIK-2)	A1899 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	8.1 µM (XO)	[103]
	A293 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	18.1 µM (XO)	[10,15]
	Propafenone	296.1% activation at 100 µM (XO, MC)	75.4 µM (XO)	[75]
	Quinidine	57.7% activation at 100 µM (XO)	n.m.	[75]
	Mexiletine	20.6% activation at 100 µM (XO)	n.m.	[75]
	Verapamil	20.5% inhibition at 100 µM (XO)	n.m.	[75]
	Amiodarone	12.5% inhibition at 100 µM (XO)	n.m.	[75]
	Sotalol	9.8% inhibition at 100 µM (XO)	n.m.	[75]
	Ranolazine	8.3–34.88% inhibition at 100–300 µM (XO)	n.m.	[75,109]
	Barium	81.2–82.8% inhibition at 2 mM (XO)	n.m.	[67,72,73]
	Cesium	No significant effect at 1–2 mM (XO)	n.m.	[67,73]
	Arachidonic acid	No significant effect at 100 µM (XO)	n.m.	[67,73]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Genistein	No significant effect at 100 µM (XO)	n.m.	[85]
	Carvedilol	No significant effect at 100 µM (XO)	n.m.	[75]
	Amitriptyline	No significant effect at 100 µM (XO)	n.m.	[75]
	Ajmaline	No significant effect at 100 µM (XO)	n.m.	[75]
	Vernakalant	No significant effect at 100 µM (XO)	n.m.	[83]
	Dronedarone	No significant effect at 100 µM (XO)	n.m.	[82]
	Digoxin	No significant effect (XO)	n.m.	[111]
	Digitoxin	No significant effect (XO)	n.m.	[111]
	Metoprolol	17.3% activation at 100 µM (XO)	n.m.	[75]
	Propranolol	139.2% activation at 100 µM (XO)	n.m.	[75]
	Bupivacaine	25.7% inhibition at 1 mM (XO)	n.m.	[73]
	TEA	19.9% inhibition at 1 mM (XO)	n.m.	[67]
	Quinine	17.8% inhibition at 1 mM (XO)	n.m.	[73]
	Lidocaine	13.1% inhibition at 1 mM (XO)	n.m.	[73]
	4-AP	No significant effect at 0.1–2 mM (XO)	n.m.	[67,73]
	Chloroform	44.7% inhibition at 800 µM (XO)	n.m.	[67]
	Halothane	56.4% inhibition at 800 µM (XO)	n.m.	[67]
	Isoflurane	58.4% activation at 800 µM (XO)	n.m.	[67]
K_2P18.1 (TRESK)	Vernakalant	Activation (XO, MC)	40 µM (MC)	[83]
	Isoflurane	Activation (XO)	162 µM (XO)	[61]
	Sevoflurane	Activation (XO)	224 µM (XO)	[61]
	Halothane	Activation (XO)	300 µM (XO)	[61]
	Desflurane	Activation (XO)	658 µM (XO)	[61]
	Dronedarone	29% activation at 100 µM (XO)	n.m.	[82]
	Loratadine	Inhibition (MC)	490 nM (MC)	[126]
	A1899 (High affinity K_2P3.1 inhibitor)	Inhibition (XO)	900 nM (XO)	[103]
	Cloxiquine	Inhibition (MC)	3.2 µM (MC)	[130]
	Zinc	Inhibition (XO)	5–10 µM for the murine but not the human ortholog	[131]
	Arachidonic acid	43% inhibition at 20 µM (MC)	6.6 µM (MC)	[73,78]
	Lamotrigine	Inhibition (MC)	47 µM (MC)	[132]
	Bupivacaine	~75% inhibition at 100 µM (MC)	80.4 µM (XO)	[61,133]
	Tetracaine	Inhibition (XO)	496 µM (XO)	[61]
	Ropivacaine	Inhibition (XO)	610 µM (XO)	[61]
	Chlorprocaine	Inhibition (XO)	832 µM (XO)	[61]
	Mepivacaine	Inhibition (XO)	1300 µM (XO)	[61]
	Lidocaine	~70–75% inhibition at 1 mM (MC)	3.4 mM (XO)	[61,73,78]
	Mibefradil	Inhibition at 3 µM (XO)	n.m.	[131]
	Quinidine	49% inhibition at 10 µM (MC)	n.m.	[133]
	Linoleic acid	~35% inhibition at 20 µM (MC)	n.m.	[78]
	Oleatic acid	~50% inhibition at 20 µM (MC)	n.m.	[78]
	Docosahexaenoic acid	~60% inhibition at 20 µM (MC)	n.m.	[78]
	Propafenone	95% inhibition at 50 µM (MC)	n.m.	[78]
	Glyburide	76% inhibition at 50 µM (MC)	n.m.	[78]
	Quinidine	90% inhibition at 100 µM (MC)	n.m.	[78]
	Quinine	41.9–75% inhibition at 100 µM (MC)	n.m.	[61,78]
	Etomidate	30.5% inhibition at 100 µM (XO)	n.m.	[61]
	Pentobarbital	10.4% inhibition at 100 µM (XO)	n.m.	[61]
	Ketamine	14.5% inhibition at 100 µM (XO)	n.m.	[61]
	Alphaxalone	45.4% inhibition at 100 µM (XO)	n.m.	[61]
	Gabapentin	4.2% inhibition at 100 µM (XO)	n.m.	[61]
	Barium	38% inhibition at 3 mM (MC)	n.m.	[78,133]
	Ethanol	~15% inhibition at 150 mM (MC)	n.m.	[61,133]
	Apamin	No significant effect at 100 nM (XO)	n.m.	[133]
	Ruthenium red	No significant effect at 5 µM (MC)	n.m.	[133]
	Glibenclamide	No significant effect at 10 µM (MC)	n.m.	[133]
	Stearic acid	No significant effect at 20 µM (MC)	n.m.	[78]
	Digoxin	No significant effect at 100 µM (XO)	n.m.	[111]
	Digitoxin	No significant effect at 100 µM (XO)	n.m.	[111]
	Flecainide	No significant effect at 100 µM (XO)	n.m.	[84]
	Genistein	No significant effect at 100 µM (XO)	n.m.	[85]
	Tolazamide	No significant effect at 100 µM (MC)	n.m.	[78]
	Glipizide	No significant effect at 100 µM (MC)	n.m.	[78]
	Paxilline	No significant effect at 100 µM (MC)	n.m.	[78]
	Penitrem A	No significant effect at 100 µM (MC)	n.m.	[78]
	Ranolazine	No significant effect at 300 µM (XO)	n.m.	[109]
	Cesium	No significant effect at 1 mM (MC)	n.m.	[133]
	4-AP	No significant effect at 1 mM (XO)	n.m.	[73,78]
	TEA	No significant effect at 1 mM (XO) 30% inhibition at 2 mM (MC)	n.m.	[61,73,78]
	Mercury	Inhibition (XO)	n.m.	[131]
	Tetrapentyl-ammonium	Inhibition (MC)	n.m.	[130]

Potency of different drugs or compounds to activate or inhibit heterologously expressed K_2P currents. Compounds that are used as experimental high-affinity inhibitors of individual K_2P channels are highlighted in bold. Please note, however, that these compounds are by no means completely specific for single members of the K_2P family. IC50, mean inhibitory concentration; MC, mammalian cells; n.m., not measured; XO, Xenopus laevis oocytes.