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]
-
mAChR1 Verwandte Produkte (120)
Verwandte Produkte (120)
-
Solifenacin
0 ImagesSynonyms: YM905 free baseSolifenacin (YM905 free base) is a novel muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively.
-
Sabcomeline hydrochloride
0 ImagesSynonyms: SB-202026 hydrochloride; Memric hydrochlorideSabcomeline (SB-202026; Memric) hydrochloride is a muscarinic receptor agonist capable of crossing the blood-brain barrier. Sabcomeline hydrochloride exhibits affinity for all hM1 to hM5 subtypes (pKi=6.72-7.23), and shows near-full agonism at the hM3 receptor, inducing extracellular acidification. Sabcomeline hydrochloride alters the binding kinetics of dopamine D2 receptors through neural network regulation. Sabcomeline hydrochloride also causes minimal cardiovascular changes, effectively reverses spatial memory deficits in rodents and induces conditioned taste aversion. Sabcomeline hydrochloride is an important tool compound in studies of Alzheimer's disease and related neurodegenerative diseases.
-
Smilagenin
0 ImagesSmilagenin (SMI) is a small-molecule steroidal sapogenin from Anemarrhena asphodeloides and Pelargonium hortorum widely used in traditional Chinese medicine for treating chronic neurodegeneration diseases. Smilagenin (SMI) improves memory of aged rats by increasing the muscarinic receptor subtype 1 (M1)-receptor density. Smilagenin (SMI) attenuates Aβ(25-35)-induced neurodegenerationvia stimulating the gene expression of brain-derived neurotrophic factor, may represents a novel therapeutic strategy for AD.
-
(Rac)-5-Hydroxymethyl Tolterodine
0 ImagesSynonyms: (Rac)-Desfesoterodine; (Rac)-PNU-200577(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.
-
VU0357017 hydrochloride
0 ImagesSynonyms: CID-25010775VU0357017 hydrochloride (CID-25010775) is a potent, selective and brain-penetrant allosteric agonist of M1 muscarinic acetylcholine receptor, with an EC50 of 477 nM. VU0357017 hydrochloride is highly selective for M1 and has no activity at M2-M5 up to the highest concentrations tested (30 μM). VU0357017 hydrochloride can be used for the research of Alzheimer’s disease and schizophrenia.
-
N-Desmethylclozapine
0 ImagesSynonyms: Norclozapine; Desmethylclozapine; NormethylclozapineN-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.
-
McN-A-343
0 ImagesMcN-A-343 is a selective M1 muscarinic agonist that stimulates muscarinic transmission in sympathetic ganglia. McN-A-343 produces a significant inhibitory effect on Muscarine (HY-121404)-evoked catecholamine secretion from the isolated perfused rat adrenal gland. McN-A-343 is involved in the regulation of neuronal firing and activates enteroendocrine L cells to release glucagon-like peptide 1 (GLP-1) and modulates the secretion of α-melanocyte stimulating hormone (α-MSH) from the pituitary gland in the central nervous system. McN-A-343 reduces colonic inflammation and oxidative stress in Acetic acid (HY-Y0319)-induced ulcerative colitis (UC) mice. McN-A-343 can be used for the study of ulcerative colitis.
-
Biperiden hydrochloride
0 ImagesBiperiden (KL 373) hydrochloride is a non-selective muscarinic receptor antagonist that competitively binds to M1 muscarinic receptors, thereby inhibiting acetylcholine and enhancing dopamine signaling in the central nervous system. Biperiden hydrochloride has the potential for the research of Parkinson's disease and other related psychiatric disorders.
-
Imidafenacin
0 ImagesSynonyms: KRP-197; ONO-8025Imidafenacin (KRP-197; ONO-8025) is an orally active inhibitor of muscarinic (mAChR) M1 and M3 receptors. Imidafenacin potently inhibits bladder contraction in vivo and exerts an antidiuretic effect by enhancing the signaling pathway of vasopressin (antidiuretic hormone). Imidafenacin can be used in research related to overactive bladder.
-
Telenzepine dihydrochloride
0 ImagesTelenzepine dihydrochloride is a selective and orally active muscarinic M1 receptor antagonist with a Ki of 0.94 nM. Telenzepine dihydrochloride inhibits gastric acid secretion and has antiulcer effects.
-
VU0364572 TFA
0 ImagesVU0364572 TFA is an orally active and selective allosteric agonist of the M1 muscarinic receptor with an EC50 of 0.11 μM. VU0364572 TFA has neuroprotective potential for preventing memory impairments and reducing neuropathology in Alzheimer’s Disease. VU0364572 TFA is CNS penetrant.
-
Dicyclomine hydrochloride
0 ImagesDicyclomine hydrochloride is a potent and orally active muscarinic cholinergic receptors antagonist. Dicyclomine hydrochloride shows high affinity for muscarinic M1 receptor subtype (Ki=5.1 nM) and M2 receptor subtype (Ki=54.6 nM) in brush-border membrane and basal plasma membranes, respectively. Dicyclomine is an antispasmodic agent and relieves smooth muscle spasm of the gastrointestinal tract in vivo.
-
VU0467319
0 ImagesSynonyms: VU319VU0467319 (Compound VU319) is a highly selective and blood-brain-permeable, orally active M1 positive allosteric modulator (PAM) (EC50: 492 nM). VU0467319 is selective (EC50 > 30 μM) versus M2-5 for both human and rat. VU0467319 improves cognitive impairment in Alzheimer's disease (AD) through central M1 muscarinic receptors. VU0467319 does not induce cholinergic adverse reactions and has potential in AD research.
-
Solifenacin Succinate
0 ImagesSynonyms: YM905Solifenacin Succinate (YM905) is a novel muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively.
-
Solifenacin hydrochloride
0 ImagesSynonyms: YM905 hydrochlorideSolifenacin hydrochloride (YM905 hydrochloride) is a muscarinic receptor antagonist, with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively.
-
Tiotropium bromide monohydrate
0 ImagesSynonyms: BA-679 BR monohydrateTiotropium bromide monohydrate (BA-679 BR monohydrate) is a long-acting anticholinergic bronchodilator. Tiotropium bromide monohydrate blocks the action of acetylcholine at muscarinic M1, M2, and M3 receptors, prevents bronchoconstriction, and dilates bronchial airways. Tiotropium bromide monohydrate is applicable to research related to chronic obstructive pulmonary disease and asthma.
-
TBPB
0 ImagesTBPB (tert-butyl peroxybenzoate) is a highly selective, blood-brain-permeable M1 mAChR allosteric agonist (EC50=289 nM) with anti-schizophrenia and anti-inflammatory activities. TBPB can enhance the sensitivity of M1 receptors to acetylcholine, activate downstream signaling pathways, and inhibit the release of pro-inflammatory cytokines (TNF-α, IL-6). TBPB can regulate the processing of amyloid and can be used in the study of neurodegenerative diseases (such as Alzheimer's disease) and inflammation-related diseases (such as sepsis).
