Iperoxo (iodide)
目录号 : GC43906An agonist of muscarinic acetylcholine receptors
Cas No.:247079-84-1
Sample solution is provided at 25 µL, 10mM.
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Iperoxo is an agonist of muscarinic acetylcholine receptors. It stimulates [35S]GTPγS binding to CHO cell membranes expressing human M2 muscarinic receptors and cell membranes expressing M4 muscarinic receptors (EC50s = 2.12 and 8.47 nM, respectively). Iperoxo induces M1-dependent inhibition of the twitch response in electrically-stimulated isolated rabbit vas deferens (pD2 = 9.87) and M3-mediated contraction of isolated guinea pig ileum (pD2 = 9.78). In vivo, iperoxo reduces formalin-induced paw licking and acetic acid-induced writhing in mice (ED50s = 0.004 and 0.001 mg/kg, respectively).
Cas No. | 247079-84-1 | SDF | |
Canonical SMILES | C[N+](C)(C)CC#CCOC1=NOCC1.[I-] | ||
分子式 | C10H17N2O2•I | 分子量 | 324.2 |
溶解度 | Water: 5 mg/ml (warmed) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 3.0845 mL | 15.4226 mL | 30.8452 mL |
5 mM | 0.6169 mL | 3.0845 mL | 6.169 mL |
10 mM | 0.3085 mL | 1.5423 mL | 3.0845 mL |
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给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
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2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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Structural Features of Iperoxo-BQCA Muscarinic Acetylcholine Receptor Hybrid Ligands Determining Subtype Selectivity and Efficacy
ACS Chem Neurosci 2022 Jan 5;13(1):97-111.PMID:34905693DOI:10.1021/acschemneuro.1c00572.
Selective agonists for the human M1 and M4 muscarinic acetylcholine receptors (mAChRs) are attractive candidates for the treatment of cognitive disorders, such as Alzheimer's disease and schizophrenia. Past efforts to optimize a ligand for selective agonism at any one of the M1-M5 mAChR subtypes has proven to be a significant challenge. Recently, research efforts have demonstrated that hybrid ligands may offer a potential solution to the lack of selectivity at mAChRs. In an attempt to design M1 mAChR selective agonists by hybridizing an M1 mAChR selective positive allosteric modulator [1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid] and a potent agonist [(4-[(4,5-dihydro-3-isoxazolyl)oxy]-N,N,N-trimethyl-2-butyn-1-aminium iodide) (Iperoxo)], we unexpectedly discovered that these ligands possessed noticeable M2/M4 mAChR selectivity. Evaluation of truncated derivatives of the hybrid ligands at the M1-M5 mAChR subtypes suggests that the allosteric pharmacophore of iperoxo-based mAChR hybrid ligands likely sterically disrupts the allosteric site of the mAChRs, attenuating the efficacy of M1/M3/M5 mAChR responses compared to M2/M4 mAChRs, resulting in a preference for the M2/M4 mAChRs. However, at certain intermediate linker lengths, the effects of this apparent disruption of the allosteric site are diminished, restoring nonselective agonism and suggesting a possible allosteric interaction which is favorable to efficacy at all M1-M5 mAChRs.