Target family: Acetylcholine receptors (muscarinic) (type: gpcr)
Target: M<sub>5</sub> receptor

Ligand: pirenzepine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Median affinity: 7.1 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: revefenacin (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2018)
Primary target: no
Median affinity: 8.199999809265137 pKi
Reference (Journal): Pharmacological properties of revefenacin (TD-4208), a novel, nebulized long-acting, and lung selective muscarinic antagonist, at human recombinant muscarinic receptors and in rat, guinea pig, and human isolated airway tissues.
Published in: Pharmacol Res Perspect

Ligand: sabcomeline (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 7.1 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: scopolamine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1953)
Primary target: no
Median affinity: 8.699999809265137 pKi
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: (S)-dimetindene (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 6.119999885559082 pKi
Reference (Journal): Structure-activity relationships of dimethindene derivatives as new M2-selective muscarinic receptor antagonists.
Published in: J Med Chem

Ligand: silahexocyclium (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.7 pKi
Reference (Journal): Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells.
Published in: Mol Pharmacol

Ligand: solifenacin (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2004), UK (2009)
Primary target: no
Median affinity: 7.199999809265137 pKi
Reference (Journal): AE9C90CB: a novel, bladder-selective muscarinic receptor antagonist for the treatment of overactive bladder.
Published in: Br J Pharmacol

Ligand: strychnine (Natural product)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Median affinity: 3.6 pKd
Reference (Journal): Detection, quantitation, and verification of allosteric interactions of agents with labeled and unlabeled ligands at G protein-coupled receptors: interactions of strychnine and acetylcholine at muscarinic receptors.
Published in: Mol Pharmacol

Ligand: [3H]acetylcholine (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  -

Ligand: [3H]iperoxo (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 8.300000190734863 pKd
Reference (Journal): New insight into active muscarinic receptors with the novel radioagonist [³H]iperoxo.
Published in: Biochem Pharmacol

Ligand: [3H]N-methyl scopolamine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): High level stable expression of pharmacologically active human M1-M5 muscarinic receptor subtypes in mammalian cells.
Published in: Biotechnol Lett

Ligand: [3H]N-methyl scopolamine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist.
Published in: J Pharmacol Exp Ther

Ligand: [3H]N-methyl scopolamine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
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: [3H]N-methyl scopolamine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): Crystal structure of the M<sub>5</sub> muscarinic acetylcholine receptor.
Published in: Proc Natl Acad Sci USA

Ligand: [3H]N-methyl scopolamine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): Interaction of neuromuscular blocking drugs with recombinant human m1-m5 muscarinic receptors expressed in Chinese hamster ovary cells.
Published in: Br J Pharmacol

Ligand: [3H]N-methyl scopolamine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): Subtype selectivity of the positive allosteric action of alcuronium at cloned M1-M5 muscarinic acetylcholine receptors.
Published in: J Pharmacol Exp Ther

Ligand: [3H]N-methyl scopolamine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): Application of transfected cell lines in studies of functional receptor subtype selectivity of muscarinic agonists.
Published in: J Pharmacol Exp Ther

Ligand: [3H]QNB (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): Subtype selectivity of the positive allosteric action of alcuronium at cloned M1-M5 muscarinic acetylcholine receptors.
Published in: J Pharmacol Exp Ther

Ligand: tiotropium (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2004)
Primary target: no
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: tiotropium (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2004)
Primary target: no
Median affinity:  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: tolterodine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1998)
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: tolterodine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1998)
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: tripitramine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 7.5 pKi
Reference (Journal): Binding profile of the selective muscarinic receptor antagonist tripitramine.
Published in: Eur J Pharmacol

Ligand: tropicamide (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1960)
Primary target: no
Median affinity: 6.400000095367432 pKi
Reference (Journal): Characterization of PCS1055, a novel muscarinic M4 receptor antagonist.
Published in: Eur J Pharmacol

Ligand: UH-AH 37 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.300000190734863 pKi
Reference (Journal): Selectivity profile of the novel muscarinic antagonist UH-AH 37 determined by the use of cloned receptors and isolated tissue preparations.
Published in: Br J Pharmacol

Ligand: UH-AH 37 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.300000190734863 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: umeclidinium (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2013), EMA (2014)
Primary target: no
Median affinity: 9.899999618530273 pKi
Reference (Journal): Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases.
Published in: J Pharmacol Exp Ther

Ligand: VU0119498 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 5.400000095367432 pEC50
Reference (Journal): Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins.
Published in: J Med Chem

Ligand: VU0238429 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 5.940000057220459 pEC50
Reference (Journal): Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins.
Published in: J Med Chem

Ligand: VU0255035 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 5.599999904632568 pKi
Reference (Journal): A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning.
Published in: Mol Pharmacol

Ligand: xanomeline (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Structural basis of efficacy-driven ligand selectivity at GPCRs.
Published in: Nat Chem Biol

Ligand: xanomeline (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors.
Published in: Br J Pharmacol

Ligand: xanomeline (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Journal): Persistent binding and functional antagonism by xanomeline at the muscarinic M5 receptor.
Published in: J Pharmacol Exp Ther

Ligand: xanomeline (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
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