Table 1.

K_2P inhibitors^{171–192,194}

Green indicates structurally validated inhibitors. Yellow indicates inhibitors supported by mutagenesis or mutagenesis combined with simulation studies. Cells used to measure activity are indicated as follows:

^aOocytes,

^bHEK cells,

^cCHO Cells,

^dThallium flux assay,

^eCOS-7 cells,

^ftsA201 cells, AZF cells,

^hhippocampal pyramidal neurons,

ⁱLysosome flux assay.

^*Only K_2Ps tested against the inhibitor are listed.

^†Other SSRIs such as citalopram and paroxetine inhibit K_2Ps and likely bind to the fenestration site.

^‡Other structurally similar local anesthetics such as lidocaine, ropivacaine, mepivacaine and etidocaine likely bind K_2Ps similarly to bupivacaine.

^§Many K_V1.5 blockers have been identified as being more potent antagonists for TASK channels. In addition to A1899 and A293, ICAGEN-4, MSD-D and A1899 derivatives have all been shown to potently inhibit TASK channels.

^ǁK_2Ps are traditionally insensitive to quaternary ammoniums applied extracellularly, however are sensitive to intracellular application. Quaternary ammoniums with longer alkyl chains inhibit K_2Ps more strongly than those with short alkyl chains.

^**Both typical antipsychotics and atypical antipsychotics (fluphenazine, haloperidol, loxapine, clozapine, etc.) have been shown to modulate K_2P channels.

^††Other dihydropyridines such as niguldipine and nifedipine antagonize TREK channels.

^‡‡K_2P2.1 (TREK-1) was first reported to be insensitive to 3 μM anandamide,¹⁹⁵ however this was contested by Liu et al.¹⁹³