Potassium channel opener

A potassium channel opener is a type of drug which facilitates ion transmission through potassium channels.

Examples

Some examples include:

• Diazoxide[1] vasodilator used for hypertension, smooth muscle relaxing activity
• Minoxidil[2] vasodilator used for hypertension, also used to treat hair loss
• Nicorandil[3] vasodilator used to treat angina
• Pinacidil[4]
• Retigabine,[5][6] an anticonvulsant
• Flupirtine, analgesic with muscle relaxant and anticonvulsant properties

Class	Subclasses	Activators
Calcium-activated 6T & 1P	BK channel SK channel IK channel	^[citation needed] 1-EBIO NS309 CyPPA BKCa-specific: Flufenamic acid Meclofenamic acid Niflumic acid Nimesulide Rottlerin (mallotoxin) Tolfenamic acid
Inwardly rectifying 2T & 1P	ROMK (Kir1.1)	^[citation needed] none
	GPCR regulated (Kir3.x)	^[citation needed] GPCR agonists^[example needed] ML-297 (VU0456810)
	ATP-sensitive (Kir6.x)	^[citation needed] Aprikalim Bimakalim Cromakalim Diazoxide Emakalim Levcromakalim Mazokalim Minoxidil Naminidil Nicorandil Pinacidil Rilmakalim Sarakalim
Tandem pore domain 4T & 2P	TWIK (TWIK-1, TWIK-2, KCNK7)[7][8] TREK (TREK-1, TREK-2, TRAAK[9])[7][8] TASK (TASK-1, TASK-3, TASK-5)[7][8] TALK (TASK-2,[10] TALK-1, TALK-2)[7][8] THIK (THIK-1, THIK-2)[7][8] TRESK[7][8][11][12]	^[citation needed] halothane[13][14][15] Riluzole Arachidonic acid[9]
Voltage-gated 6T & 1P	hERG (Kv11.1) KvLQT1 (Kv7.1)	KCNQ (Kv7)-specific: Flupirtine Retigabine (Kv7)[16] XEN1101[17]

See also

• Potassium channel blocker

References

1. Mizutani S, Prasad SM, Sellitto AD, Schuessler RB, Damiano RJ, Lawton JS (August 2005). "Myocyte volume and function in response to osmotic stress: observations in the presence of an adenosine triphosphate-sensitive potassium channel opener". Circulation. 112 (9 Suppl): I219–23. doi:10.1161/CIRCULATIONAHA.104.523746. PMID 16159820.
2. Wang T (February 2003). "The effects of the potassium channel opener minoxidil on renal electrolytes transport in the loop of henle". J. Pharmacol. Exp. Ther. 304 (2): 833–40. doi:10.1124/jpet.102.043380. PMID 12538840. S2CID 6948410.
3. Sudo H, Yogo K, Ishizuka N, Otsuka H, Horie S, Saito K (November 2008). "Nicorandil, a potassium channel opener and nitric oxide donor, improves the frequent urination without changing the blood pressure in rats with partial bladder outlet obstruction". Biol. Pharm. Bull. 31 (11): 2079–82. doi:10.1248/bpb.31.2079. PMID 18981577.
4. Stojnic N, Gojkovic-Bukarica L, Peric M, et al. (June 2007). "Potassium channel opener pinacidil induces relaxation of the isolated human radial artery". J. Pharmacol. Sci. 104 (2): 122–9. doi:10.1254/jphs.FP0061434. PMID 17538231. ^[dead link‍]
5. Rundfeldt C (October 1997). "The new anticonvulsant retigabine (D-23129) acts as an opener of K+ channels in neuronal cells". European Journal of Pharmacology. 336 (2–3): 243–9. doi:10.1016/S0014-2999(97)01249-1. PMID 9384239.
6. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA (August 2000). "Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine". Molecular Pharmacology. 58 (2): 253–62. doi:10.1124/mol.58.2.253. PMID 10908292. S2CID 11112809.
7. Enyedi P, Czirják G (Apr 2010). "Molecular background of leak K+ currents: two-pore domain potassium channels" (PDF). Physiological Reviews. 90 (2): 559–605. doi:10.1152/physrev.00029.2009. PMID 20393194. S2CID 9358238.
8. Lotshaw DP (2007). "Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels". Cell Biochemistry and Biophysics. 47 (2): 209–56. doi:10.1007/s12013-007-0007-8. PMID 17652773. S2CID 12759521.
9. Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M (Jun 1998). "A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids". The EMBO Journal. 17 (12): 3297–308. doi:10.1093/emboj/17.12.3297. PMC 1170668. PMID 9628867.
10. Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N (Mar 2001). "Potassium leak channels and the KCNK family of two-P-domain subunits". Nature Reviews. Neuroscience. 2 (3): 175–84. doi:10.1038/35058574. PMID 11256078. S2CID 9682396.
11. Sano Y, Inamura K, Miyake A, Mochizuki S, Kitada C, Yokoi H, Nozawa K, Okada H, Matsushime H, Furuichi K (Jul 2003). "A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord". The Journal of Biological Chemistry. 278 (30): 27406–12. doi:10.1074/jbc.M206810200. PMID 12754259. S2CID 22656809.
12. Czirják G, Tóth ZE, Enyedi P (Apr 2004). "The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin" (PDF). The Journal of Biological Chemistry. 279 (18): 18550–8. doi:10.1074/jbc.M312229200. PMID 14981085. S2CID 21219622.
13. Meadows HJ, Randall AD (Mar 2001). "Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel". Neuropharmacology. 40 (4): 551–9. doi:10.1016/S0028-3908(00)00189-1. PMID 11249964. S2CID 20181576.
14. Patel AJ, Honoré E, Lesage F, Fink M, Romey G, Lazdunski M (May 1999). "Inhalational anesthetics activate two-pore-domain background K+ channels". Nature Neuroscience. 2 (5): 422–6. doi:10.1038/8084. PMID 10321245. S2CID 23092576.
15. Gray AT, Zhao BB, Kindler CH, Winegar BD, Mazurek MJ, Xu J, Chavez RA, Forsayeth JR, Yost CS (Jun 2000). "Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5". Anesthesiology. 92 (6): 1722–30. doi:10.1097/00000542-200006000-00032. PMID 10839924. S2CID 45487917.
16. Rogawski MA, Bazil CW (Jul 2008). "New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels". Current Neurology and Neuroscience Reports. 8 (4): 345–52. doi:10.1007/s11910-008-0053-7. PMC 2587091. PMID 18590620.
17. Premoli I, Rossini PG, Goldberg PY, Posadas K, Green L, Yogo N, Pimstone S, Abela E, Beatch GN, Richardson MP (November 2019). "TMS as a pharmacodynamic indicator of cortical activity of a novel anti-epileptic drug, XEN1101". Annals of Clinical and Translational Neurology. 6 (11): 2164–2174. doi:10.1002/acn3.50896. PMC 6856596. PMID 31568714. XEN1101 is a novel positive allosteric modulator ("opener") of the potassium channel KCNQ2/3 (Kv7.2/7.3) currently being developed by Xenon Pharmaceuticals Inc. for the treatment of focal epilepsy.