Target family: Acetylcholine receptors (muscarinic) (type: gpcr)
Target: M<sub>4</sub> receptor

Ligand: 3-quinuclidinyl-benzilate (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 10.399999618530273 pKi
Reference (Journal): Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha2A-Adrenoceptors In Vitro.
Published in: Invest Ophthalmol Vis Sci

Ligand: 4-DAMP (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.899999618530273 pKi
Reference (Journal): Antagonist binding profiles of five cloned human muscarinic receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: 4-DAMP (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.1 pKi
Reference (Journal): Cloning of the rat M3, M4 and M5 muscarinic acetylcholine receptor genes by the polymerase chain reaction (PCR) and the pharmacological characterization of the expressed genes.
Published in: Life Sci

Ligand: (+)-aceclidine (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 5.4 pEC50
Reference (Journal): The interaction of the enantiomers of aceclidine with subtypes of the muscarinic receptor.
Published in: J Pharmacol Exp Ther

Ligand: (-)-aceclidine (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 4.8 pEC50
Reference (Journal): The interaction of the enantiomers of aceclidine with subtypes of the muscarinic receptor.
Published in: J Pharmacol Exp Ther

Ligand: acetylcholine (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Published in: Mol Pharmacol

Ligand: acetylcholine (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Reverse engineering of the selective agonist TBPB unveils both orthosteric and allosteric modes of action at the M₁ muscarinic acetylcholine receptor.
Published in: Mol Pharmacol

Ligand: aclidinium (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA and EMA (2012)
Primary target: no
Median affinity: 10 pKi
Reference (Journal): Azaindole N-methyl hydroxamic acids as HIV-1 integrase inhibitors-II. The impact of physicochemical properties on ADME and PK.
Published in: Bioorg Med Chem Lett

Ligand: AE9C90CB (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 9.5 pKi
Reference (Journal): AE9C90CB: a novel, bladder-selective muscarinic receptor antagonist for the treatment of overactive bladder.
Published in: Br J Pharmacol

Ligand: AFDX384 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Antagonist binding profiles of five cloned human muscarinic receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: AFDX384 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Characterization of PCS1055, a novel muscarinic M4 receptor antagonist.
Published in: Eur J Pharmacol

Ligand: alcuronium (Natural product)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Median affinity: 5.6 pKd
Reference (Journal): Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Published in: Mol Pharmacol

Ligand: amitriptyline (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1961)
Primary target: yes
Median affinity: 8.140000343322754 pKi
Reference (Journal): Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics.
Published in: Biochem Pharmacol

Ligand: AQ-RA 741 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Antagonist binding profiles of five cloned human muscarinic receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: AQ-RA 741 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Comparison of the in vitro and in vivo profiles of tolterodine with those of subtype-selective muscarinic receptor antagonists.
Published in: Eur J Pharmacol

Ligand: arecaidine propargyl ester (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 5.9 pKi
Reference (Journal): Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Published in: Mol Pharmacol

Ligand: arecoline (Natural product)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: no
Median affinity: 5.5 pKi
Reference (Journal): Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Published in: Mol Pharmacol

Ligand: arecoline (Natural product)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: no
Median affinity: 5.5 pKi
Reference (Journal): Human muscarinic receptors expressed in A9L and CHO cells: activation by full and partial agonists.
Published in: Br J Pharmacol

Ligand: arecoline (Natural product)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: no
Median affinity: 5.5 pKi
Reference (Journal): Enhanced arecoline derivatives as muscarinic acetylcholine receptor M1 ligands for potential application as PET radiotracers.
Published in: Eur J Med Chem

Ligand: atropine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1973)
Primary target: yes
Median affinity:  pKi
Reference (Journal): Characterization of PCS1055, a novel muscarinic M4 receptor antagonist.
Published in: Eur J Pharmacol

Ligand: atropine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1973)
Primary target: yes
Median affinity:  pKi
Reference (Journal): Receptor binding studies of soft anticholinergic agents.
Published in: AAPS PharmSci

Ligand: atropine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1973)
Primary target: no
Median affinity: 9.699999809265137 pKi
Reference (Journal): Cloning of the rat M3, M4 and M5 muscarinic acetylcholine receptor genes by the polymerase chain reaction (PCR) and the pharmacological characterization of the expressed genes.
Published in: Life Sci

Ligand: atropine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1973)
Primary target: yes
Median affinity:  pKi
Reference (Journal): Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.
Published in: EMBO J

Ligand: atropine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1973)
Primary target: yes
Median affinity:  pKi
Reference (Journal): Pharmacological properties of (2R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide: a novel mucarinic antagonist with M(2)-sparing antagonistic activity.
Published in: J Pharmacol Exp Ther

Ligand: bethanechol (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: FDA (no history prior to 1948)
Primary target: no
Median affinity: 4 pKi
Reference (Journal): Human muscarinic receptors expressed in A9L and CHO cells: activation by full and partial agonists.
Published in: Br J Pharmacol

Ligand: bethanechol (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: FDA (no history prior to 1948)
Primary target: no
Median affinity: 4 pKi
Reference (Journal): Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Published in: Mol Pharmacol

Ligand: biperiden (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1959)
Primary target: no
Median affinity: 8.619999885559082 pKd
Reference (Journal): Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells.
Published in: J Pharmacol Exp Ther

Ligand: brucine (Natural product)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Published in: Mol Pharmacol

Ligand: brucine (Natural product)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies.
Published in: Mol Pharmacol

Ligand: brucine N-oxide (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 3.6 pKd
Reference (Journal): Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies.
Published in: Mol Pharmacol

Ligand: brucine N-oxide (Synthetic organic)
Interaction type: Allosteric modulator
Action: Neutral
Ligand approved: no
Median affinity: 3.6 pKd
Reference (Journal): Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies.
Published in: Mol Pharmacol

Ligand: carbachol (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: FDA (1972)
Primary target: no
Median affinity:  pKi
Reference (Journal): Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Published in: Mol Pharmacol

Ligand: carbachol (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: FDA (1972)
Primary target: no
Median affinity:  pKi
Reference (Journal): Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry.
Published in: Br J Pharmacol

Ligand: cevimeline (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2000)
Primary target: no
Median affinity: 5.989999771118164 pKi
Reference (Journal): SB 202026: a novel muscarinic partial agonist with functional selectivity for M1 receptors.
Published in: J Pharmacol Exp Ther

Ligand: darifenacin (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: EMA & FDA (2004)
Primary target: no
Median affinity:  pKi
Reference (Journal): AE9C90CB: a novel, bladder-selective muscarinic receptor antagonist for the treatment of overactive bladder.
Published in: Br J Pharmacol

Ligand: darifenacin (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: EMA & FDA (2004)
Primary target: no
Median affinity:  pKi
Reference (Journal): Pharmacological properties of (2R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide: a novel mucarinic antagonist with M(2)-sparing antagonistic activity.
Published in: J Pharmacol Exp Ther

Ligand: darifenacin (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: EMA & FDA (2004)
Primary target: no
Median affinity:  pKi
Reference (Journal): Comparison of the in vitro and in vivo profiles of tolterodine with those of subtype-selective muscarinic receptor antagonists.
Published in: Eur J Pharmacol

Ligand: dicyclomine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1950)
Primary target: no
Median affinity: 8.300000190734863 pKi
Reference (Journal): Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha2A-Adrenoceptors In Vitro.
Published in: Invest Ophthalmol Vis Sci

Ligand: dosulepin (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Primary target: no
Median affinity: 7.210000038146973 pKi
Reference (Journal): Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics.
Published in: Biochem Pharmacol

Ligand: furtrethonium (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 4.3 pKi
Reference (Journal): Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Published in: Mol Pharmacol

Ligand: glycopyrrolate (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1961), EMA (2012)
Primary target: yes
Median affinity:  pKi
Reference (Journal): The discovery of new spirocyclic muscarinic M3 antagonists.
Published in: Bioorg Med Chem Lett

Ligand: glycopyrrolate (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1961), EMA (2012)
Primary target: yes
Median affinity:  pKi
Reference (Journal): The Influence of receptor kinetics on the onset and duration of action and the therapeutic index of NVA237 and tiotropium.
Published in: J Pharmacol Exp Ther

Ligand: Gö 7874 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Neutral
Ligand approved: no
Median affinity: 5.7 pKd
Reference (Journal): Allosteric interactions of staurosporine and other indolocarbazoles with N-[methyl-(3)H]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site.
Published in: Mol Pharmacol

Ligand: guanylpirenzepine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 6.199999809265137 pKi
Reference (Journal): Binding of the labelled muscarinic toxin 125I-MT1 to rat brain muscarinic M1 receptors.
Published in: Eur J Pharmacol

Ligand: hexahydrodifenidol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 7.1 pKi
Reference (Journal): Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells.
Published in: Mol Pharmacol

Ligand: hexahydrosiladifenidol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Stimulation of cyclic AMP accumulation and phosphoinositide hydrolysis by M3 muscarinic receptors in the rat peripheral lung.
Published in: Biochem Pharmacol

Ligand: hexahydrosiladifenidol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 7.7 pKi
Reference (Journal): Cloning of the rat M3, M4 and M5 muscarinic acetylcholine receptor genes by the polymerase chain reaction (PCR) and the pharmacological characterization of the expressed genes.
Published in: Life Sci

Ligand: hexahydrosiladifenidol (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells.
Published in: Mol Pharmacol

Ligand: hexocyclium (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.3 pKi
Reference (Journal): Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells.
Published in: Mol Pharmacol

Ligand: himbacine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Antagonist binding profiles of five cloned human muscarinic receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: himbacine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Binding and functional selectivity of himbacine for cloned and neuronal muscarinic receptors.
Published in: J Pharmacol Exp Ther

Ligand: himbacine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.399999618530273 pKi
Reference (Journal): Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha2A-Adrenoceptors In Vitro.
Published in: Invest Ophthalmol Vis Sci

Ligand: himbacine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): A toxin from the green mamba Dendroaspis angusticeps: amino acid sequence and selectivity for muscarinic m4 receptors.
Published in: FEBS Lett

Ligand: N-benzyl brucine (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Median affinity: 4.5 pKd
Reference (Journal): Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies.
Published in: Mol Pharmacol

Ligand: N-benzyl brucine (Synthetic organic)
Interaction type: Allosteric modulator
Action: Neutral
Ligand approved: no
Median affinity: 4.5 pKd
Reference (Journal): Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies.
Published in: Mol Pharmacol

Ligand: iperoxo (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  -
Reference (Journal): New insight into active muscarinic receptors with the novel radioagonist [³H]iperoxo.
Published in: Biochem Pharmacol

Ligand: p-F-HHSiD (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Receptor binding studies of soft anticholinergic agents.
Published in: AAPS PharmSci

Ligand: p-F-HHSiD (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Stimulation of cyclic AMP accumulation and phosphoinositide hydrolysis by M3 muscarinic receptors in the rat peripheral lung.
Published in: Biochem Pharmacol

Ligand: ipratropium (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1986)
Primary target: no
Median affinity: 9.199999809265137 pKi
Reference (Journal): Pharmacological properties of (2R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide: a novel mucarinic antagonist with M(2)-sparing antagonistic activity.
Published in: J Pharmacol Exp Ther

Ligand: KT 5720 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Neutral
Ligand approved: no
Median affinity: 6.4 pKd
Reference (Journal): Allosteric interactions of staurosporine and other indolocarbazoles with N-[methyl-(3)H]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site.
Published in: Mol Pharmacol

Ligand: lithocholylcholine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 5.3 pKi
Reference (Journal): Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist.
Published in: J Pharmacol Exp Ther

Ligand: LY2033298 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia.
Published in: Proc Natl Acad Sci USA

Ligand: LY2033298 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity.
Published in: Proc Natl Acad Sci USA

Ligand: LY2119620 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 5.5 pKd
Reference (Journal): Characterization of the novel positive allosteric modulator, LY2119620, at the muscarinic M(2) and M(4) receptors.
Published in: Mol Pharmacol

Ligand: McN-A-343 (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): New functionally selective muscarinic agonists.
Published in: Life Sci