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].
Verweise:
- [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 Verwandte Produkte (120)
Verwandte Produkte (120)
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Ipratropium bromide hydrate
0 ImagesSynonyms: Sch 1000 bromide hydrateIpratropium bromide (Sch 1000) hydrate 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 hydrate relaxes smooth muscle, can be used in the research for COPD (chronic obstructive pulmonary disease) and asthma.
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Penehyclidine hydrochloride
0 ImagesSynonyms: Penequinine hydrochloridePenehyclidine (Penequinine) hydrochloride, a anticholinergic agent, is a selective antagonist of M1 and M3 receptors. Penehyclidine hydrochloride activates NF-kβ in lung tissue and inhibits the release of inflammatory factors. Penehyclidine hydrochloride can alleviate the pulmonary inflammatory response in rats with chronic obstructive pulmonary disease (COPD) undergoing mechanical ventilation.
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Talsaclidine
0 ImagesSynonyms: WAL 2014 FU free baseTalsaclidine (WAL 2014 FU) is an orally active, blood-brain barrier-permeable muscarinic M1 receptor agonist. Talsaclidine activates the sympathetic nervous system and promotes adrenal catecholamine release in vivo. Talsaclidine exhibits extensive tissue distribution, kidney-dominant excretion and brain penetration properties, and it can be used in studies related to cholinergic signaling, cognitive function and Alzheimer's disease.
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Clozapine hydrochloride
0 ImagesSynonyms: HF 1854 hydrochlorideClozapine hydrochloride (HF 1854 hydrochloride) is an antipsychotic used for the research of schizophrenia. Clozapine hydrochloride has high affinity for a number of neuroreceptors. Clozapine hydrochloride is a potent antagonist of dopamine D2 with a Ki of 75 nM. Clozapine hydrochloride inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor with Kis of 9.5 nM and 4 nM, respectively. Clozapine hydrochloride is also a potent and selective agonist at the muscarinic M4 receptor (EC50=11 nM).
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Cevimeline
0 ImagesSynonyms: AF102BCevimeline (AF-102B) is a quinuclidine derivative of acetylcholine and a selective and orally active muscarinic M1 and M3 receptor agonist. Cevimeline stimulates secretion by the salivary glands and can be used as a sialogogue for xerostomia. Cevimeline can cross the blood-brain barrier (BBB).
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Olanzapine-d3
0 ImagesSynonyms: LY170053-d3Olanzapine-d3 (LY170053-d3) is the deuterium labeled Olanzapine. Olanzapine is a selective, orally active monoaminergic antagonist with high affinity binding to serotonin H1, 5HT2A/2C, 5HT3, 5HT6 (Ki=7, 4, 11, 57, and 5 nM, respectively), dopamine D1-4 (Ki=11 to 31 nM), muscarinic M1-5 (Ki=1.9-25 nM), and adrenergic α1 receptors (Ki=19 nM). Olanzapine is an atypical antipsychotic.
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Hexocyclium methylsulfate
0 ImagesHexocyclium methylsulfate is a potent mAChR antagonist with pKi values of 8.9, 7.7, 8.4, 8.8 for M1, M2, M3, and M4 subtype, respectively. Hexocyclium methylsulfate has the potential for the research of duodenal ulcer and irritable bowel syndrome.
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VU6004256
0 ImagesVU6004256 is a potent and selective M1 muscarinic positive allosteric modulator (PAM) with an EC50 value of 155 nM. VU6004256 has the potential for the research of schizophrenia.
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Aceclidine hydrochloride
0 ImagesSynonyms: Quinuclidin-3-yl acetate hydrochlorideAceclidine (Quinuclidin-3-yl acetate) hydrochloride is a modulator of M3 muscarinic acetylcholine receptor and a M1 receptor agonist (EC50: 40 μM). Aceclidine hydrochloride is a cycloplegic agent, a surfactant, a tonicity adjustor and optionally a viscosity enhancer and an antioxidant. Aceclidine hydrochloride 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.
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(Rac)-5-Hydroxymethyl Tolterodine hydrochloride
0 ImagesArt. -Nr.: HY-76570ACAS. Nr.: 250214-40-5Synonyms: (Rac)-Desfesoterodine hydrochloride; (Rac)-PNU-200577 hydrochloride(Rac)-5-Hydroxymethyl Tolterodine ((Rac)-Desfesoterodine) hydrochloride, 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 hydrochloride can be used for overactive bladder research.
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Ipratropium-d3 bromide
0 ImagesArt. -Nr.: HY-B0241SReinheit: 98.0%Synonyms: Sch 1000-d3Ipratropium-d3 (bromide) is the deuterium labeled Ipratropium bromide. Ipratropium bromide (Sch 1000) is a muscarinic receptor antagonist, with binding IC50 values of 2.9 nM, 2 nM, and 1.7 nM for M1, M2, and M3 receptors, respectively. Ipratropium bromide can be used in the research for COPD (chronic obstructive pulmonary disease) and asthma.
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Isopteropodine
0 ImagesIsopteropodine is a positive modulator that selectively acts on muscarinic M1 and 5-HT2 receptors. Isopteropodine has an EC50 of 9.92 μM for acetylcholine and 14.5 μM for 5-HT. Isopteropodine also has antibacterial activity against Gram-positive bacteria, with MICs of 150 μg/mL and 250 μg/mL for Staphylococcus aureus and Bacillus subtilis, respectively. Isopteropodine enhances receptor function by increasing the affinity of agonists for receptors and can also inhibit the growth of specific Gram-positive bacteria, and can be used in cognitive impairment and antibacterial research.
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p-F-HHSiD hydrochloride
0 ImagesSynonyms: p-Fluorohexahydrosiladifenidol hydrochloridep-F-HHSiD (p-Fluorohexahydrosiladifenidol) hydrochloride is a potent and selective M3 mAChR antagonist. p-F-HHSiD hydrochloride has antagonistic effects on other subtypes of the M receptor and the alpha1-adrenoceptor. p-F-HHSiD hydrochloride 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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Nebracetam hydrochloride
0 ImagesSynonyms: WEB 1881 FU hydrochlorideNebracetam (WEB 1881 FU) hydrochloride is an orally active M1 muscarinic receptor agonist. Nebracetam hydrochloride can induce an increase in intracellular Ca2+ concentration, with an EC50 value of 1.59 mM. Nebracetam hydrochloride exhibits neuroprotective activity and the ability to improve cognitive impairment. Nebracetam hydrochloride can be used in the research of neurological diseases such as Alzheimer's disease.
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Trihexyphenidyl-d5 hydrochloride
0 ImagesArt. -Nr.: HY-B1277SReinheit: 99.88%Trihexyphenidyl-d5 hydrochloride is deuterium labeled Trihexyphenidyl hydrochloride (HY-B1277). Trihexyphenidyl hydrochloride is a selective and orally active M1 muscarinic receptor antagonist with an IC50 of 3.7 nM for rat cerebral cortex M1 muscarinic receptors. Trihexyphenidyl hydrochloride modulates cholinergic activity, countering acetylcholine supersensitivity in neural pathways. Trihexyphenidyl hydrochloride improves movement disorder, inhibits McN-A-343 (HY-107648)-induced pressor responses, vagally-induced bradycardia and vasodilatation. Trihexyphenidyl hydrochloride can be used for the research of Parkinson's disease..
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Trospium-d8 chloride
0 ImagesArt. -Nr.: HY-B0461STrospium-d8 (chloride) is the deuterium labeled Trospium chloride. Trospium 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.
