mAChR1
mAChR1 (M1 muscarinic acetylcholine receptor) mediates acetylcholine-induced neurotransmission and is widely expressed in the central nervous system[1]. Mechanistically, M1 activates multiple signaling cascades, including Gαq/11-dependent inositol phosphate signaling, while orthosteric and allosteric agonists can produce distinct downstream coupling profiles[2]. In experimental models, M1 knockout ablates muscarinic receptor-dependent M-current regulation and reduces pilocarpine-induced seizure activity, supporting its use in neuronal excitability studies[3]. In Alzheimer’s disease research, M1 activation links cholinergic hypofunction to APP processing, Aβ production, tau phosphorylation, and learning and memory pathways[1]. Compared with related isoforms, M1 and M4 have distinct orthosteric and allosteric binding-site features, but the conserved acetylcholine pocket makes subtype-selective orthosteric ligand design difficult[4]. For experimental applications, M1 positive allosteric modulators such as BQCA and BQZ-12 restored memory loss and slowed disease progression in mouse prion disease models[5].
References:
- [1]. Jiang S, et al. M1 muscarinic acetylcholine receptor in Alzheimer's disease. Neurosci Bull. 2014 Apr;30(2):295-307. [Content Brief]
- [2]. Thomas RL, et al. G protein coupling and signaling pathway activation by m1 muscarinic acetylcholine receptor orthosteric and allosteric agonists. J Pharmacol Exp Ther. 2008 Nov;327(2):365-74. [Content Brief]
- [3]. Hamilton SE, et al. Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13311-6. [Content Brief]
- [4]. Thal DM, et al. Crystal structures of the M1 and M4 muscarinic acetylcholine receptors. Nature. 2016 Mar 17;531(7594):335-40. [Content Brief]
- [5]. Bradley SJ, et al. M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss. J Clin Invest. 2017 Feb 1;127(2):487-499. [Content Brief]
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mAChR1 Related Products (112)
Related Products (112)
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Clozapine
0 ImagesClozapine (HF 1854) is an antipsychotic used for the research of schizophrenia. Clozapine has high affinity for a number of neuroreceptors. Clozapine is a potent antagonist of dopamine D2 with a Ki of 75 nM. Clozapine inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor with Kis of 9.5 nM and 4 nM, respectively. Clozapine is also a potent and selective agonist at the muscarinic M4 receptor (EC50=11 nM).
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Xanomeline
0 ImagesSynonyms: LY-246708Xanomeline, as an effective and selective muscarinic type 1 and type 4 (M1/M4) receptor agonist, increases neuronal excitability. Xanomeline can be used for the research of neurological disorders, such as schizophrenia.
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Tiotropium Bromide
0 ImagesSynonyms: BA679 BRTiotropium bromide (BA-679 BR) is a long-acting anticholinergic bronchodilator. Tiotropium bromide blocks the action of acetylcholine at muscarinic M1, M2, and M3 receptors, prevents bronchoconstriction, and dilates bronchial airways. Tiotropium bromide is applicable to research related to chronic obstructive pulmonary disease and asthma.
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(S)-(+)-Dimethindene maleate
0 Images(S)-(+)-Dimethindene maleate, an enantiomer, is a potent M2-selective muscarinic receptor antagonist (pA2 = 7.86/7.74; pKi = 7.78). (S)-(+)-Dimethindene maleate shows lower affinities for the muscarinic M1 (pA2 = 6.83/6.36; pKi = 7.08), the M3 (pA2 = 6.92/6.96; pKi = 6.70) and the M4 receptors (pKi = 7.00), respectively. (S)-(+)-Dimethindene maleate also is a histamine H1 receptor antagonist (pA2 = 7.48).
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Vedaclidine
0 ImagesCat. No.: HY-183144CAS No.: 141575-50-0Vedaclidine is an orally active muscarinic acetylcholine receptor (mAChR) modulator with mixed receptor activity, which activates muscarinic M2 and M4 receptors and blocks muscarinic M1, M3 and M5 receptors. Vedaclidine exerts its activity through interaction with spinal M4 muscarinic receptors, and does not induce hypothermia or excessive salivation. Vedaclidine can be used in research related to pain, neuropathic pain and inflammatory pain states.
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VU0415248
0 ImagesCat. No.: HY-182587CAS No.: 1359087-83-4VU0415248 is a selective muscarinic acetylcholine receptor 1 (M1) inhibitor. VU0415248 inhibits acetylcholine-induced calcium mobilization in cells expressing human and rat M1 muscarinic acetylcholine receptors, with an IC50 of 0.4 and 0.18 μM, respectively. VU0415248 is applicable to the research of Parkinson's disease, movement disorders and fragile X syndrome.
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p-F-HHSiD
0 ImagesCat. No.: HY-137388CAS No.: 116679-83-5Synonyms: p-Fluorohexahydrosiladifenidolp-F-HHSiD (p-Fluorohexahydrosiladifenidol) is a potent and selective M3 mAChR antagonist. p-F-HHSiD has antagonistic effects on other subtypes of the M receptor and the alpha1-adrenoceptor. p-F-HHSiD can be used for the researches of cancer, metabolic, neurological and cardiovascular disease such as, colon cancer, Alzheimer’s disease and diabetes.
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Iperoxo
0 ImagesIperoxo is a potent superagonist of muscarinic acetylcholine receptor (mAChR) that activates M1, M2 and M3 receptors with pEC50 of 9.87, 10.1 and 9.78. Iperoxo can be used for direct probing activation-related conformational transitions of muscarinic receptors when labeled with tritium.
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Cevimeline hydrochloride
0 ImagesSynonyms: AF102B hydrochlorideCevimeline hydrochloride (AF102B hydrochloride) is a quinuclidine derivative of acetylcholine and a selective and orally active muscarinic M1 and M3 receptor agonist. Cevimeline hydrochloride stimulates secretion by the salivary glands and can be used as a sialogogue for xerostomia. Cevimeline hydrochloride can cross the blood-brain barrier (BBB).
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VU 0255035
0 ImagesSynonyms: VU 255035VU0255035 is a highly selective and competitive M1 mAChR antagonist. VU0255035 blocks M1 mAChR signals to reduce epileptic seizures and regulate neuronal membrane potential. VU0255035 can be used in research related to central nervous system diseases, such as epilepsy, Parkinson's disease, and dystonia.
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Trospium chloride
0 ImagesTrospium chloride is an orally active, specific and competitive antagonist of muscarinic cholinergic receptors (mAChRs), with antimuscarinic activity. Trospium chloride binds to muscarinic receptors M1, M2 and M3 with high affinity, but not nicotinic, cholinergic receptors.
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Fesoterodine fumarate
0 ImagesCat. No.: HY-A0030CAS No.: 286930-03-8Fesoterodine Fumarate is an orally active, nonsubtype selective, competitive muscarinic receptor (mAChR) antagonist with pKi values of 8.0, 7.7, 7.4, 7.3, 7.5 for M1, M2, M3, M4, M5 receptors, respectively. Fesoterodine Fumarate is used for the overactive bladder (OAB).
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Pirenzepine dihydrochloride
0 ImagesSynonyms: LS 519; Pirenzepin dihydrochloride; Gastrozepin dihydrochloridePirenzepine (LS 519) dihydrochloride is a selective M1 mAChR (muscarinic acetylcholine receptor) antagonist, with poor penetration of the blood-brain barrier. Pirenzepine dihydrochloride reduces gastric acid secretion and reduces muscle spasm, can be used in peptic ulcers research. Pirenzepine dihydrochloride shows anti-proliferative activity to cancer cells.
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TAK-071
0 ImagesTAK-071 is a novel, potent and highly selective muscarinic acetylcholine receptor 1 (M1R) positive allosteric modulator. EC50 of TAK-071 M1R agonist activities is 520 nM.
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Cevimeline hydrochloride hemihydrate
0 ImagesSynonyms: SNI-2011; AF102B hydrochloride hemihydrateCevimeline hydrochloride hemihydrate (SNI-2011) is a quinuclidine derivative of acetylcholine and a selective and orally active muscarinic M1 and M3 receptor agonist. Cevimeline hydrochloride hemihydrate stimulates secretion by the salivary glands and can be used as a sialogogue for xerostomia. Cevimeline hydrochloride hemihydrate can cross the blood-brain barrier (BBB).
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MK-7622
0 ImagesSynonyms: M1 receptor modulatorMK-7622 (M1 receptor modulator) is an orally active positive allosteric modulator of muscarinic M1 acetylcholine receptors (mAChRs). MK-7622 enhances ACh-induced calcium flux in CHO cells expressing human M1 receptors (EC50 = 21 nM) and shows robust agonist activity in rat M1-expressing CHO cells, increasing intracellular calcium. MK-7622 reverses Scopolamine (HY-N0296)-induced cognitive deficits in rhesus macaques in an object retrieval detour task. MK-7622 can be used for the study of Alzheimer's disease (AD).
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Ipratropium bromide
0 ImagesSynonyms: Sch 1000Ipratropium bromide (Sch 1000) is a muscarinic receptor antagonist, with IC50s of 2.9 nM, 2 nM, and 1.7 nM for M1, M2, and M3 receptors, respectively. Ipratropium bromide relaxes smooth muscle, can be used in the research for COPD (chronic obstructive pulmonary disease) and asthma.
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Diphenidol hydrochloride
0 ImagesDiphenidol hydrochloride (Difenidol hydrochloride) is a non-selective muscarinic M1-M4 receptor antagonist, has anti-arrhythmic activity. Diphenidol hydrochloride is also a potent non-specific blocker of voltage-gated ion channels (Na+, K+, and Ca2+) in neuronal cells. Diphenidol hydrochloride can be used in the study of antivertigo and antinausea.
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Aceclidine
0 ImagesAceclidine (Quinuclidin-3-yl acetate) is a modulator of M3 muscarinic acetylcholine receptor and a M1 receptor agonist (EC50: 40 μM). Aceclidine is a cycloplegic agent, a surfactant, a tonicity adjustor and optionally a viscosity enhancer and an antioxidant. Aceclidine has the potential for the research of disorders such as refractive errors of the eye, xerostomia, Sjogren's syndrome, glaucoma, conjunctivitis, lacrimal gland disease, and esotropia.
