muscarinic m4 receptor

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

RO1138452 (CAY10441) is a selective and orally bioavailable antagonist of prostacyclin receptor (pKi: 8.3). It antagonizes the carbaprostacyclin-induced activation of human neuroblastoma adenylate cyclase, blocking cyclic AMP accumulation in a dose-dependent manner. Likewise, it inhibits the binding of tritiated iloprost to rodent neuroblastoma cells with a Ki of about 1.5 nM. At levels between 2-20 mg/kg in rats, CAY10441 shows significant analgesic activity in standard antinociceptive assays [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.

Tropicamide (Ro 1-7683) is a synthetic muscarinic antagonist with anticholinergic properties similar to atropine. Upon ocular administration, it binds to and blocks muscarinic receptors in the sphincter and ciliary muscles, inhibiting cholinergic responses and causing pupil dilation and ciliary muscle paralysis. Tropicamide is used as a diagnostic agent to induce short-duration mydriasis and cycloplegia.

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.

PD-102807 is a selective and competitive M4 muscarinic receptor antagonist (IC50 = 90.7 nM), with IC50 values of 950–7412 nM for M1, M2, M3, and M5 receptors, and can be used for Parkinson's disease research, as well as to inhibit airway smooth muscle (ASM) contraction.

DREADD agonist 21 is a potent agonist of human muscarinic acetylcholine M3 receptors (EC50=1.7 nM).

VU0152099 is a potent and selective M4 mAChR allosteric potentiator(EC50 = 380 ± 93 nM).

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

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.

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

VU0152100 is an effective and selective allosteric potentiator of M4 mAChR (EC50: 380 ± 93 nM).

VU0467154 is a positive allosteric modulator of the M4 muscarinic acetylcholine receptor (M4 mAChR).

VU0467485 is a potent and highly selective M4 mAChR positive allosteric modulator (PAM). It enhances receptor response to acetylcholine, used for schizophrenia and cognitive research.

Direclidine is a positive allosteric modulator of the muscarinic M4 receptor (muscarinic M4 receptor).

VU6016235 is a structurally unique, orally available, and highly selective tricyclic M4 muscarinic acetylcholine receptor positive allosteric modulator.

Clozapine (HF 1854) dihydrochloride is utilized for researching psychiatric disorders. This compound exhibits high affinity for numerous neuroreceptors and acts as an effective antagonist of dopamine receptors, with a Ki value of 75 nM. Clozapine inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor, with Ki values of 9.5 nM and 4 nM, respectively. Additionally, Clozapine is a selective agonist of the muscarinic M4 receptor (EC50 = 11 nM).

Muscarinic M4 modulator-1 is a positive allosteric modulator of the Muscarinic M4 receptor. It activates the muscarinic M4 receptor with allosteric efficacy (EC50) values of 14 nM in CHO-K1 cells and 3 nM in HEK293 cells. Muscarinic M4 modulator-1 exhibits antipsychotic-like activity and shows potential for research in psychiatric and/or neurological disorders.

VU6002703 (Compound 17) is a brain-penetrant positive allosteric modulator (PAM) of the M4 muscarinic acetylcholine receptor (mAChR), exhibiting an EC50 of 0.6 μM for hM4. This compound is useful for researching neuropsychiatric disorders and rare genetic central nervous system conditions.

M4mAChRModulator-2 is an orally active and selective positive allosteric modulator (PAM) of the M4 muscarinic acetylcholine receptor (M4mAChR) capable of crossing the blood-brain barrier, with an EC50 of 513 nM. It demonstrates high target selectivity, showing minimal affinity and low inhibition rates for non-target receptors (D1R/D2R/D3R, 5-HT subtypes, κ/δ/μ opioid receptors, H1, M1/M2), while specifically binding to M4mAChR with a Ki of 377 nM and an inhibition rate of 62.8%. Additionally, M4mAChRModulator-2 can reverse the hyperlocomotion induced by Dizocilpine (MK-801) in mice and is applicable for schizophrenia research.

M3mAChRagonist 1 is a dual positive allosteric modulator (PAM) that primarily targets the M3 subtype of M3/M5 mAChRs. It demonstrates high subtype selectivity over other mAChR subtypes, including M1, M2, and M4. By modulating the M3 muscarinic acetylcholine receptor, M3mAChRagonist 1 enhances the signaling pathway, leading to increased contraction of isolated rat bladder strips.

VU6009453 (compound 15q) is a brain-penetrant positive allosteric modulator (PAM) of the M4 muscarinic acetylcholine receptor (M4mAChR), with an EC50 of 383 nM. It is utilized in research related to neurological disorders.

AF-DX 384 free base is a selective and efficient M2 muscarinic acetylcholine receptor (M2 mAChR) and M4 muscarinic acetylcholine receptor (M4 mAChR) antagonist. It can be used for research on neurodegenerative diseases like Parkinson's.

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