Target family: Inwardly rectifying potassium channels (K<sub>IR</sub>) (type: vgic)
Target: K<sub>ir</sub>3.2

Ligand: amitriptyline (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1961)
Median affinity: 4 pIC50
Reference (Journal): Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
Published in: Neuropsychopharmacology

Ligand: bupivacaine (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1972), EMA (2020)
Median affinity:  pIC50
Reference (Journal): Mechanism underlying bupivacaine inhibition of G protein-gated inwardly rectifying K+ channels.
Published in: Proc Natl Acad Sci USA

Ligand: clomipramine (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1989)
Median affinity: 4.4 pIC50
Reference (Journal): Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
Published in: Neuropsychopharmacology

Ligand: clozapine (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1989)
Primary target: no
Median affinity: 3.799999952316284 pEC50
Reference (Journal): Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes.
Published in: Br J Pharmacol

Ligand: desipramine (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: FDA (no history prior to 1964)
Primary target: no
Median affinity: 4.400000095367432 pIC50
Reference (Journal): Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
Published in: Neuropsychopharmacology

Ligand: dizocilpine (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: no
Median affinity: 3.7 pIC50
Reference (Journal): Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells.
Published in: Neuron

Ligand: ethanol (Metabolite)
Interaction type: Activator
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  -
Reference (Journal): Ethanol opens G-protein-activated inwardly rectifying K+ channels.
Published in: Nat Neurosci

Ligand: ethanol (Metabolite)
Interaction type: Activator
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  -
Reference (Journal): A discrete alcohol pocket involved in GIRK channel activation.
Published in: Nat Neurosci

Ligand: ethanol (Metabolite)
Interaction type: Activator
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  -
Reference (Journal): G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action.
Published in: Nat Neurosci

Ligand: F3 (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: no
Median affinity: 4.1 pIC50
Reference (Journal): Differential effects of general anesthetics on G protein-coupled inwardly rectifying and other potassium channels.
Published in: Anesthesiology

Ligand: fluoxetine (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1987)
Primary target: no
Median affinity:  pIC50
Reference (Journal): Inhibition of G protein-activated inwardly rectifying K+ channels by fluoxetine (Prozac).
Published in: Br J Pharmacol

Ligand: haloperidol (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1967)
Median affinity: 4.1 pEC50
Reference (Journal): Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes.
Published in: Br J Pharmacol

Ligand: halothane (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1958)
Median affinity: 4.2 pIC50
Reference (Journal): G protein-gated inwardly rectifying potassium channels are targets for volatile anesthetics.
Published in: Mol Pharmacol

Ligand: imipramine (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1959)
Median affinity: 4.3 pIC50
Reference (Journal): Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
Published in: Neuropsychopharmacology

Ligand: maprotiline (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1980)
Median affinity: 4 pIC50
Reference (Journal): Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
Published in: Neuropsychopharmacology

Ligand: Na+ (Inorganic)
Interaction type: Activator
Action: Agonist
Ligand approved: no
Median affinity: 1.6 pEC50
Reference (Journal): Molecular determinants for sodium-dependent activation of G protein-gated K+ channels.
Published in: J Biol Chem

Ligand: nortriptyline (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1964)
Median affinity: 3.9 pIC50
Reference (Journal): Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
Published in: Neuropsychopharmacology

Ligand: pimozide (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1984)
Primary target: no
Median affinity: 5.5 pEC50
Reference (Journal): Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes.
Published in: Br J Pharmacol

Ligand: PIP2 (Metabolite)
Interaction type: Activator
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 6.300000190734863 pKd
Reference (Journal): Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
Published in: Nature

Ligand: QX-314 (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Median affinity: 3.7 pIC50
Reference (Journal): Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells.
Published in: Neuron

Ligand: SCH-23390 (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pIC50
Reference (Journal): Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels.
Published in: Mol Pharmacol

Ligand: thioridazine (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1962)
Median affinity: 4.2 pEC50
Reference (Journal): Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes.
Published in: Br J Pharmacol

Ligand: verapamil (Synthetic organic)
Interaction type: Gating inhibitor
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1981)
Primary target: no
Median affinity: 3.9000000953674316 pIC50
Reference (Journal): Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells.
Published in: Neuron