Target family: Dopamine receptors (type: gpcr)
Target: D<sub>4</sub> receptor

Ligand: A-381393 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: yes
Median affinity: 8.819999694824219 pKi
Reference (Journal): 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist.
Published in: Neuropharmacology

Ligand: A412997 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 8.100000381469727 pKi
Reference (Journal): A-412997 is a selective dopamine D4 receptor agonist in rats.
Published in: Pharmacol Biochem Behav

Ligand: A412997 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: no
Median affinity: 8.100000381469727 pKi
Reference (Journal): A-412997 is a selective dopamine D4 receptor agonist in rats.
Published in: Pharmacol Biochem Behav

Ligand: ABT-670 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: yes
Median affinity: 5.840000152587891 pKi
Reference (Journal): Discovery of 3-methyl-N-(1-oxy-3',4',5',6'-tetrahydro-2'H-[2,4'-bipyridine]-1'-ylmethyl)benzamide (ABT-670), an orally bioavailable dopamine D4 agonist for the treatment of erectile dysfunction.
Published in: J Med Chem

Ligand: apomorphine (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: yes
Approval source: EMA (2001), FDA (2004)
Primary target: yes
Median affinity: 8.399999618530273 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: aripiprazole (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2002), EMA (2004)
Median affinity: 7.3 pKi
Reference (Journal): Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.
Published in: Mol Pharmacol

Ligand: benperidol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: UK (2006)
Primary target: no
Median affinity: 10.180000305175781 pKi
Reference (Journal): Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors.
Published in: Mol Psychiatry

Ligand: bromocriptine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1978)
Primary target: yes
Median affinity: 6.400000095367432 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: (+)-butaclamol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 6.3 pKi
Reference (Journal): Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor.
Published in: Mol Pharmacol

Ligand: cabergoline (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: yes
Approval source: FDA (1996)
Median affinity: 7.3 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: chlorpromazine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1957)
Median affinity: 7.8 pKi
Reference (Journal): Dopamine D4 versus D2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications.
Published in: Eur J Pharmacol

Ligand: clozapine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1989)
Median affinity: 7.5 pKi
Reference (Journal): Dopamine D4 versus D2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications.
Published in: Eur J Pharmacol

Ligand: CP-226269 (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 9.4 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: CP-293019 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.5 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: dopamine (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: FDA (1974)
Median affinity: 7.4 pKi
Reference (Journal): Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.
Published in: Mol Pharmacol

Ligand: dopamine (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: FDA (1974)
Primary target: yes
Median affinity: 7.599999904632568 pKi
Reference (Journal): Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.
Published in: Nature

Ligand: eticlopride (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 7 pKi
Reference (Journal): Is clozapine selective for the dopamine D4 receptor?
Published in: Life Sci

Ligand: FAUC213 (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 9 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: FAUC213 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: fenoldopam (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: FDA (1997)
Median affinity: 6.5 pKi
Reference (Journal): Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.
Published in: Nature

Ligand: haloperidol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1967)
Primary target: yes
Median affinity:  pKi
Reference (Journal): Asenapine: a novel psychopharmacologic agent with a unique human receptor signature.
Published in: J Psychopharmacol (Oxford)

Ligand: haloperidol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1967)
Primary target: yes
Median affinity:  pKi
Reference (Journal): Characterization of the binding of SCH 39166 to the five cloned dopamine receptor subtypes.
Published in: Pharmacol Biochem Behav

Ligand: haloperidol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1967)
Primary target: yes
Median affinity:  pKi
Reference (Journal): Dopamine D4 versus D2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications.
Published in: Eur J Pharmacol

Ligand: L741742 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.5 pKi
Reference (Journal): 5-(4-Chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)isoxazole: a potent, selective antagonist at human cloned dopamine D4 receptors.
Published in: J Med Chem

Ligand: L745870 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 9.40999984741211 pKi
Reference (Journal): 3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor.
Published in: J Med Chem

Ligand: L-750,667 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 10 pKi
Reference (Journal): Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.
Published in: Mol Pharmacol

Ligand: lisuride (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: yes
Approval source: EMA (2011)
Median affinity: 8.3 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: loxapine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1975), EMA (2013)
Primary target: yes
Median affinity: 8.109999656677246 pKi
Reference (Journal): Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors.
Published in: Neuropsychopharmacology

Ligand: ML398 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: yes
Median affinity: 7.440000057220459 pKi
Reference (Journal): Discovery and Characterization of ML398, a Potent and Selective Antagonist of the D4 Receptor with in Vivo Activity.
Published in: ACS Med Chem Lett

Ligand: nafadotride (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 6.4 pKi
Reference (Journal): Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.
Published in: Mol Pharmacol

Ligand: nemonapride (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 10 pKd
Reference (Journal): Low density of dopamine D4 receptors in Parkinson's, schizophrenia, and control brain striata.
Published in: Synapse

Ligand: NGD 94-1 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.5 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: PD168,077 (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity: 8.800000190734863 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: pergolide (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: yes
Approval source: FDA (1988)
Median affinity: 7.2 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: perospirone (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Primary target: yes
Median affinity: 10.050000190734863 pKi
Reference (Journal): Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors.
Published in: Mol Psychiatry

Ligand: PF-592379 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 5.380000114440918 pIC50
Reference (Journal): Lack of abuse potential in a highly selective dopamine D3 agonist, PF-592,379, in drug self-administration and drug discrimination in rats.
Published in: Behav Pharmacol

Ligand: piribedil (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 6.5 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: prochlorperazine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1956)
Primary target: no
Median affinity: 6.090000152587891 pKi
Reference (Webpage): National Toxicology Program: Dept of Health and Human Services.

Ligand: quinpirole (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 7.5 pKi
Reference (Journal): Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.
Published in: Nature

Ligand: quinpirole (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 7.5 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: quinpirole (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 7.5 pKi
Reference (Journal): Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor.
Published in: Mol Pharmacol

Ligand: raclopride (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 5.7 pKi
Reference (Journal): Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.
Published in: Mol Pharmacol

Ligand: RBI257 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.6 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: Ro 10-4548 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 7.8 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: rotigotine (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: EMA (2006), FDA (2007)
Primary target: no
Median affinity: 7.260000228881836 pKi
Reference (Journal): Affinity for dopamine D2, D3, and D4 receptors of 2-aminotetralins. Relevance of D2 agonist binding for determination of receptor subtype selectivity.
Published in: J Med Chem

Ligand: roxindole (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 8.2 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: sertindole (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Primary target: yes
Median affinity:  pKi
Reference (Journal): Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors.
Published in: Mol Psychiatry

Ligand: sertindole (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Primary target: yes
Median affinity:  pKi
Reference (Journal): Antipsychotic drugs, dopamine receptors, and schizophrenia.
Published in: Clinical Neuroscience Research

Ligand: sertindole (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Primary target: yes
Median affinity:  pKi
Reference (Journal): Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors.
Published in: Neuropsychopharmacology

Ligand: sertindole (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Primary target: yes
Median affinity:  pKi
Reference (Journal): Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist.
Published in: J Pharmacol Exp Ther

Ligand: sonepiprazole (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.9 pKi
Reference (Journal): Substituted 4-aminopiperidines having high in vitro affinity and selectivity for the cloned human dopamine D4 receptor.
Published in: Eur J Pharmacol

Ligand: sonepiprazole (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.7 pKi
Reference (Journal): Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain.
Published in: Mol Pharmacol

Ligand: spiperone (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.3 pKi
Reference (Journal): Is clozapine selective for the dopamine D4 receptor?
Published in: Life Sci

Ligand: (+)-sulpiride (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 5.66 pKi
Reference (Journal): Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor.
Published in: Mol Pharmacol

Ligand: (-)-sulpiride (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Median affinity:  pKi
Reference (Journal): Pharmacological and functional characterization of D2, D3 and D4 dopamine receptors in fibroblast and dopaminergic cell lines.
Published in: J Pharmacol Exp Ther

Ligand: (-)-sulpiride (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Median affinity:  pKi
Reference (Journal): Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor.
Published in: Mol Pharmacol

Ligand: [125I]L750667 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.8 pKd
Reference (Journal): Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor.
Published in: Mol Pharmacol

Ligand: [3H]N-methylspiperone (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.5 pKi
Reference (Journal): Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.
Published in: Mol Pharmacol

Ligand: [3H]NGD941 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.3 pKd
Reference (Journal): II. Localization and characterization of dopamine D4 binding sites in rat and human brain by use of the novel, D4 receptor-selective ligand [3H]NGD 94-1.
Published in: J Pharmacol Exp Ther

Ligand: [3H]spiperone (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.5 pKd
Reference (Journal): Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.
Published in: Nature

Ligand: [3H]spiperone (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.5 pKd
Reference (Journal): Differential effects of [3H]nemonapride and [3H]spiperone binding on human dopamine D4 receptors.
Published in: Neurosci Lett

Ligand: terguride (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Median affinity: 8.1 pKi
Reference (Journal): Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: trifluoperazine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1959)
Primary target: no
Median affinity: 7.360000133514404 pKi
Reference (Journal): Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors.
Published in: Neuropsychopharmacology

Ligand: U101958 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.899999618530273 pKi
Reference (Journal): Substituted 4-aminopiperidines having high in vitro affinity and selectivity for the cloned human dopamine D4 receptor.
Published in: Eur J Pharmacol

Ligand: WAY-100635 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: no
Median affinity: 7.800000190734863 pKi
Reference (Journal): Design, synthesis, radiolabeling, and in vitro and in vivo evaluation of bridgehead iodinated analogues of N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635) as potential SPECT ligands for the 5-HT1A receptor.
Published in: J Med Chem

Ligand: zotepine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Primary target: no
Median affinity: 7.409999847412109 pKi
Reference (Journal): Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
Published in: Psychopharmacology (Berl.)