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 (121)
Related Products (121)
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Penehyclidine
0 ImagesCat. No.: HY-142119CAS No.: 87827-02-9Penehyclidine, a anticholinergic agent, is a selective antagonist of M1 and M3 receptors. Penehyclidine activates NF-kβ in lung tissue and inhibits the release of inflammatory factors. Penehyclidine can alleviate the pulmonary inflammatory response in rats with chronic obstructive pulmonary disease (COPD) undergoing mechanical ventilation.
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(Rac)-5-Hydroxymethyl Tolterodine-d14
0 ImagesCat. No.: HY-76570SCAS No.: 1185071-13-9Synonyms: (Rac)-Desfesoterodine-d14; (Rac)-PNU-200577-d14(Rac)-5-Hydroxymethyl Tolterodine-d14 is the deuterium labeled (Rac)-5-Hydroxymethyl Tolterodine. (Rac)-5-Hydroxymethyl Tolterodine ((Rac)-Desfesoterodine), an active metabolite of Tolterodine, is a mAChR antagonist (Ki values of 2.3 nM, 2 nM, 2.5 nM, 2.8 nM, and 2.9 nM for M1, M2, M3, M4, and M5 receptors, respectively). (Rac)-5-Hydroxymethyl Tolterodine can be used for overactive bladder research.
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Hexahydrosiladifenidol
0 ImagesCat. No.: HY-189031CAS No.: 98299-40-2Hexahydrosiladifenidol is a muscarinic receptor antagonist. Hexahydrosiladifenidol blocks sympathetic ganglion M1 and brainstem M2 muscarinic receptors.
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rel-Biperiden EP impurity A-d5
0 ImagesCat. No.: HY-13204S2rel-Biperiden EP impurity A-d5 is deuterium labeled Biperiden (hydrochloride).
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Solifenacin D5 hydrochloride
0 ImagesCat. No.: HY-135329CAS No.: 1426174-05-1Solifenacin D5 hydrochloride is a deuterium labeled Solifenacin hydrochloride. Solifenacin hydrochloride is a muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively.
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Milameline hydrochloride
0 ImagesCat. No.: HY-107650CAS No.: 139886-04-7Synonyms: CI 979 hydrochloride; RU 35926 hydrochlorideMilameline (CI 979; RU35926) hydrochloride is a nonselective, partical and orally active muscarinic receptor agonist that improves cognition. Milameline hydrochloride has equal affinity for different subtypes of human muscarinic receptors with IC50 of 1.3 µM for M1-, 1.1 µM for M2-, 1.5 µM for M3-, and 1.9 µM for M4-muscarinic receptors. Milameline hydrochloride has a higher affinity for sites [3H]CMD (IC50 = 20 nM), than [3H]QNB, (IC50 = 3059 nM). Milameline hydrochloride produces both central and peripheral cholinergic effects and reverses the cognitive deficits induced by Scopolamine (HY-N0296). Milameline hydrochloride can be used for the study of Alzheimer’s Disease.
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HTL-9936
0 ImagesCat. No.: HY-148961CAS No.: 1438242-59-1HTL-9936 is an orally active partial agonist of muscarinic M1 receptor. HTL-9936 has an EC50 of 32 nM for human M1 receptor and an EC50 of 224 nM for human M4 receptor. HTL-9936 activates Gq/11 coupling, promotes inositol phosphate accumulation, ERK1/2 phosphorylation, β-arrestin recruitment and receptor internalization. HTL-9936 can be used in the research of Alzheimer's disease and schizophrenia.
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M1/M4 muscarinic agonist 1
0 ImagesCat. No.: HY-149702M1/M4 muscarinic agonist 1 (compound 41) is a selective muscarinic M4/M1 agonist with EC50 values of 14 and 55 nM for M4 and M1, respectively. M1/M4 muscarinic agonist 1 can be used for research on mental diseases, such as schizophrenia, delusional disorder, etc.
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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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THRX160209
0 ImagesCat. No.: HY-189013CAS No.: 832082-44-7THRX160209 is a dual-site antagonist of the M2 muscarinic acetylcholine receptor with M2 receptor subtype selectivity. THRX160209 binds simultaneously to the orthosteric site and a spatially distinct allosteric site, competitively inhibiting receptor activation at the acetylcholine binding pocket. THRX160209 exhibits affinity for all five muscarinic receptor subtypes. THRX160209 can be used in research related to neurological disorders.
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VU6052254
0 ImagesVU6052254, a derivative of VU0467319 (HY-173396), is a selective, potent, orally active and brain-penetrant muscarinic M1 acetylcholine receptor (mAChR1) positive allosteric modulator with an EC50 of 59 nM. VU6052254 has no activity on the M2-5 receptor (EC50 > 30 μM). VU6052254 can improve memory recognition ability and reverse the cognitive impairment induced by Scopolamine (HY-N0296) with minimum effective dose both of 1 mg/kg. VU6052254 can be used for the research of neurological disease, such as Alzheimer's disease.
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N-Desmethylclozapine-d8
0 ImagesSynonyms: Norclozapine-d8; Desmethylclozapine-d8; Normethylclozapine-d8N-Desmethylclozapine-d8 is the deuterium labeled N-Desmethylclozapine. N-Desmethylclozapine is a major active metabolite of the atypical antipsychotic agent Clozapine. N-Desmethylclozapine is a potent, allosteric and partial M1 receptors agonist (EC50=115 nM) and is able to potentiate hippocampal N-methyl-d-aspartate (NMDA) receptor currents through M1 receptor activation. N-Desmethylclozapine is also a δ-opioid agonist.
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Lu AE51090
0 ImagesLu AE51090 is selective muscarinic M1 receptor agonist with blood-brain barrier penetration. Lu AE51090 activates human M1 receptor with EC50 of 61 nM, while showing no significant agonism at M2-M5 receptors. Lu AE51090 exerts procognitive effects in mice. Lu AE51090 can be used for the study of Alzheimer’s disease (AD) and cognitive impairment associated with schizophrenia (CIAS).
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M1 mAChR modulator-1
0 ImagesCat. No.: HY-177498CAS No.: 2247999-07-9M1 mAChR modulator-1 (Example 66) is a muscarinic M1 receptor (mAChR1) positive allosteric modulator. M1 mAChR modulator-1 effectively promotes gastrointestinal motility and defecation in mouse models with low central permeability. M1 mAChR modulator-1 can be used for constipation research.
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YM-58790 free base
0 ImagesCat. No.: HY-101679ACAS No.: 168830-70-4YM-58790 free base is a potent antagonist of mAChR. YM-58790 free base binds M1, M2, M3 with Ki values of 28 nM, 260 nM, and 15 nM. YM-58790 free base exhibits potent inhibitory activity on bladder pressuer in reflexly-evoked rhythmic contraction in rats.
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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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Insecticidal agent 41
0 ImagesCat. No.: HY-189402CAS No.: 3127631-07-3Insecticidal agent 41 is a potent agonist of muscarinic acetylcholine receptors (mAChRs) (with an EC50 of 2.73 μM for M1 mAChR) and an insecticide (LC50 = 42.0 mg/L). Insecticidal agent 41 binds to and agonizes insect mAChRs, induces intracellular calcium influx, and causes mosquitoes to become hyperexcitable, paralyzed, and eventually die. Insecticidal agent 41 can be used in the research and development of mosquito insecticides.
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Pirenzepine-d8
0 ImagesCat. No.: HY-17037SCAS No.: 1189944-02-2Synonyms: LS 519-d8 free base; Pirenzepin-d8; Gastrozepin-d8Pirenzepine-d8 is the deuterium labeled Pirenzepine dihydrochloride. Pirenzepine dihydrochloride (LS519) is a selective M1 muscarinic receptor antagonist.
