Compound 40 is a selective M1/M4 muscarinic antagonist with an IC50 of 19 nM for M1 receptors and 42 nM for M4 receptors [1].

Clozapine N-oxide is the major metabolite of Clozapine and is blood-brain barrier permeable. Clozapine N-oxide is an agonist of DREADDs and activates the DREADD receptors hM3Dq and hM4Di. Clozapine N-oxide is also a dopamine antagonist and selective muscarinic M4 receptor agonist.

(Rac)-Sabcomeline ((Rac)-SB-202026) is an M1/M4 muscarinic agonist used in the study of neurologic disorders such as schizophrenia.

M4 mAChR agonist-1 (4-Piperidinecarboxamide, 1-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)-) is an effective agonist of M4 mAChR (EC50 >10 μM).

VU0238441 is agonist of Muscarinic acetylcholine receptor M5 (human) with EC50 of 2.1μM.

LAS190792 (AZD8999) is a dual-action chemical compound that simultaneously acts as a strong muscarinic antagonist and β2-adrenoceptor agonist. It exhibits significant potency across a range of receptors, with pIC50 values of 8.9 for M1, 8.8 for M2, 8.8 for M3, 9.2 for M4, 8.2 for M5, 7.5 for β1, 9.1 for β2, and 5.6 for β3. Its effectiveness across these receptors makes LAS190792 a viable candidate for bronchodilator applications [1].

Methoctramine is a selective antagonist of M2 muscarinic acetylcholine receptors (IC50 = 6.1 nM in CHO-K1 cell membranes).[1] It is selective for M2 over M1, M3, M4, and M5 receptors (IC50s = 92, 770, 260, and 217 nM, respectively). In vitro, methoctramine inhibits acetylcholine-induced reductions in isolated guinea pig tracheal tube contractions when used at a concentration of 1 μM.[2] In vivo, methoctramine inhibits bradycardia and bronchoconstriction induced by acetylcholinein guinea pigs with ED50 values of 38 and 81 nmol/kg, respectively. In a rat model of spinal cord injury, methoctramine suppresses bladder overactivity induced by the non-selective muscarinic acetylcholine receptor agonist oxotremorine M.[3]

Emraclidine (CVL-231) is a muscarinic M4 receptor positive allosteric modulator and can be used in neurological diseases studies.

Muscarinic toxin 3 (MT3), a potent non-competitive antagonist of mAChR and adrenoceptors, exhibits pIC50 values of 6.71 for M1, 8.79 for M4, 8.86 for α1A, 7.57 for α1B, 8.13 for α1D, 8.49 for α2A, <6.5 for α2B, and 7.29 for α2C receptors. MT3 notably demonstrates significant adrenoceptor activity [1].

PCS1055 dihydrochloride is an effective, selective, and competitive muscarinic M4 receptor antagonist (IC50: 18.1 nM and a Kd: 5.72 nM). PCS1055 dihydrochloride is also a potent AChE inhibitor (IC50 s: 22 nM and 120 nM for electric eel and human AChE, res

VU6005806 is a potent positive allosteric modulator (PAM) of muscarinic acetylcholine receptor subtype 4 (M4) (EC50s: 94 nM, 28 nM, 87 nM, and 68 nM for human, rat, dog, and cyno M4, respectively), and used in the study of neuropsychiatric disorders.

Fesoterodine fumarate (Toviaz) is the fumarate salt form of fesoterodine, a competitive muscarinic receptor antagonist with muscle relaxant and urinary antispasmodic properties. Fesoterodine is rapidly hydrolyzed in vivo into its active metabolite 5-hydroxymethyl tolterodine, which binds and inhibits muscarinic receptors on the bladder detrusor muscle, thereby preventing bladder contractions or spasms caused by acetylcholine.

VU0467485 is a potent and selective muscarinic acetylcholine receptor 4 positive allosteric modulator. VU0467485 potentiates the activity of ACh at M4 (EC50s: 26.6 nM and 78.8 nM at the rat and human M4 receptors, respectively). VU0467485 displays selecti

Xanomeline (LY 246708), a potent agonist of muscarinic M1/M4 receptors, exhibits antipsychotic-like activity and enhances neuronal excitability. It is a valuable compound for studying schizophrenia.

Atropine Oxide is a derivative of Atropine. Atropine is a competitive antagonist of the muscarinic acetylcholine receptor types M1, M2, M3, M4, and M5. Atropine is a medication to treat certain types of nerve agents and pesticide poisonings as well as som

Imidafenacin metabolite M4 is a metabolite of the muscarinic acetylcholine receptor antagonist imidafenacin.1It is formed from imidafenacin by the cytochrome P450 (CYP) isoform CYP3A4. 1.Kanayama, N., Kanari, C., Masuda, Y., et al.Drug-drug interactions in the metabolism of imidafenacin: Role of the human cytochrome P450 enzymes and UDP-glucuronic acid transferases, and potential of imidafenacin to inhibit human cytochrome P450 enzymesXenobiotica37(2)139-154(2007)

Thiochrome is a selective enhancer of M4 muscarinic receptor of acetylcholine (ACh) affinity.

VU0467154 is a positive allosteric modulator of the M4 muscarinic acetylcholine receptor. The response to ACh with pEC50s of 7.75, 6.2, and 6 for a rat, human, and cynomolgus monkey M4 receptor, respectively.

M4 muscarinic receptor antagonist

LY2119620 is a specific, and allosteric agonist of human M2 and M4 muscarinic acetylcholine receptors.

Arecaidine propargyl ester is an agonist of M2muscarinic acetylcholine receptors (mAChRs).1It selectively binds to M2over M1, M3, M4, and M5mAChRs in CHO cells expressing the human receptors (Kis = 0.0871, 1.23, 0.851, 0.977, and 0.933 μM, respectively). Arecaidine propargyl ester induces contractions in isolated guinea pig atrium (pD2= 8.67). It induces apoptosis and the production of reactive oxygen species (ROS) in U87 and U251 glioblastoma cells when used at a concentration of 100 μM.2Arecaidine propargyl ester decreases mean arterial blood pressure in normotensive cats (ED25= 1.9 nmol/kg).3It is toxic to house flies (Musca) when administered at a dose of 75 μg/fly.4 1.Scapecchi, S., Matucci, R., Bellucci, C., et al.Highly chiral muscarinic ligands: the discovery of (2S,2’R,3’S,5’R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonistJ. Med. Chem.49(6)1925-1931(2006) 2.Di Bari, M., Tombolillo, B., Conte, C., et al.Cytotoxic and genotoxic effects mediated by M2 muscarinic receptor activation in human glioblastoma cellsNeurochem. Int.90261-270(2015) 3.Porsius, A.J., and Van Zwieten, P.A.Central action of some cholinergic drugs (arecaidine esters) and nicotine on blood pressure and heart rate of catsProg. Brain Res.47131-135(1977) 4.Honda, H., Tomizawa, M., and Casida, J.E.Insect muscarinic acetylcholine receptor: Pharmacological and toxicological profiles of antagonists and agonistsJ. Agric. Food Chem.55(6)2276-2281(2007)

Atropine Oxide is a derivative of Atropine. Atropine is a medication to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate and to decrease saliva production during surgery. Atropine is a competitive antagonist of the muscarinic acetylcholine receptor types M1, M2, M3, M4 and M5. It is classified as an anticholinergic drug (parasympatholytic).

Diphenidol hydrochloride (Difenidol hydrochloride), a muscarinic antagonist, is employed as an anti-vertigo and as an antiemetic drug.

Tropicamide (Ro 1-7683) is a synthetic muscarinic antagonist with actions similar to atropine and with an anticholinergic property. Upon ocular administration, tropicamide binds to and blocks the muscarinic receptors in the sphincter and ciliary muscle in the eye. This inhibits the responses from cholinergic stimulation, producing dilation of the pupil and paralysis of the ciliary muscle. Tropicamide is a diagnostic agent and is used to produce short-duration mydriasis and cycloplegia.

VU6000918 is a positive allosteric modulator that targets the muscarinic acetylcholine receptor subtype M4. It exhibits a half maximal effective concentration (EC50) of 19 nM for the human M4 receptor.

(S)-(+)-Dimethindene maleate is an orally available, selective muscarinic M2 receptor and histamine H1 receptor antagonist that inhibits muscarinic M1, M3, and M4 receptors.

MK-6884, a positive allosteric modulator (PAM) of M4 muscarinic receptors, exhibits a high affinity (Ki = 0.19 nM). It is a valuable compound for the investigation of neurodegenerative diseases. Additionally, MK-6884 can be efficiently radiolabeled with carbon-11, enabling its use as a PET imaging agent.