<i>N</i>-Benzylpiperidine Derivatives as α7 Nicotinic Receptor Antagonists

Criado, Manuel; Mulet, José; Sala, Francisco; Sala, Salvador; Colmena, Inés; Gandı́a, Luis; Aguilera, Óscar; Samadi, Abdelouahid; Chioua, Mourad; Marco‐Contelles, José

doi:10.1021/acschemneuro.6b00122

Cited by 8 publications

(4 citation statements)

References 44 publications

(69 reference statements)

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“…The anticholinesterase ASS234 (Fig. 13), which was developed as a therapeutic for Alzheimer disease (Romero et al, 2020), was shown to be a noncompetitive antagonist of a7 and was used as a starting point to develop additional antagonists, with compound 38 proposed as a new lead compound (Criado et al, 2016). Compound 7i (Fig.…”

Section: A7 Antagonistsmentioning

confidence: 99%

“…propoxy]-1-methyl-1H-indol-2-ylgmethyl)-N-methyl-2-propyn-1-amine(Criado et al, 2016); compound 38, 2-(1-benzylpiperidin-4-yl)ethan-1-amine(Criado et al, 2016); compound 7i, N-((1-benzylpiperidin-4-yl)methyl)-1-(2chlorobenzyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide (Peng et al, 2010); B10, 3-(4-bromophenyl)-8-methyl-1-oxa-2,4,8-triazaspiro[4.5]dec-2-ene (Zhang et al, 2020a); mecamylamine, N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine;hydrochloride; tkP3BzPB, 1,2,4,5-tetra-f5-[1-(3-benzyl)pyridinium]pent-1-ylgbenzene tetrabromide; and MLA. Therapeutic Targeting of a7 nAChR…”

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confidence: 99%

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Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors

Papke

Horenstein

2021

Pharmacol Rev

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Section: A7 Antagonistsmentioning

confidence: 99%

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confidence: 99%

Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors

Papke

Horenstein

2021

Pharmacol Rev

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“…Its antagonists (e.g., d ‐tubocurarine or snake's neurotoxin) exert an inhibitory effect on tumors. However, the reagents used in rats cannot be used in clinical settings because of their high toxicity 12‐15 …”

Section: Introductionmentioning

confidence: 99%

“…However, the reagents used in rats cannot be used in clinical settings because of their high toxicity. [12][13][14][15] Meanwhile, 7 nAChR, as a crucial receptor of neuroimmune networks, is observed in multiple immunocytes, such as M s and lymphocytes. The cholinergic anti-inflammatory pathway (CAP) is among the manifestations in neuroimmune networks.…”

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confidence: 99%

Inhibitory effect of sinomenine on lung cancer cells via negative regulation of α7 nicotinic acetylcholine receptor

Bai

Wen

Hou

et al. 2020

Journal of Leukocyte Biology

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Lung cancer is the leading cause of cancer deaths worldwide, with a high morbidity and less than 20% survival rate. Therefore, new treatment strategies and drugs are needed to reduce the mortality of patients with lung cancer. 7 nicotinic acetylcholine receptor (7 nAChR), as a receptor of nicotine and its metabolites, is a potential target for lung cancer treatment. Our previous studies revealed that sinomenine plays anti-inflammation roles via 7 nAChR and down-regulates the expression of this receptor, thus increasing the inflammatory response. Hence, sinomenine is possibly a natural ligand of this receptor. In the present study, the effects of sinomenine on lung cancer A549 cells and tumor-bearing mice were determined to investigate whether this alkaloid has an inhibitory effect on lung cancer via 7 nAChR. CCK-8 assay, wound-healing test, and flow cytometry were performed for cell proliferation, cell migration, and apoptosis analysis in vitro, respectively. Xenograft mice were used to evaluate the effects of sinomenine in vivo. Results showed that sinomenine decreased cell proliferation and migration abilities but increased the percentage of apoptotic cells. Tumor volume in tumor-bearing mice was significantly reduced after sinomenine treatment compared with that in the vehicle group mice (p < 0.05). Furthermore, the effects of sinomenine were abolished by the 7 nAChR antagonist mecamylamine and the allosteric modulator PNU-120596, but no change occurred when the mice were pretreated with the muscarinic acetylcholine receptor antagonist atropine. Meanwhile, sinomenine suppressed 7 nAChR expression in vitro and in vivo, as well as the related signaling molecules pERK1/2 and ERK1/2 and the transcription factors TTF-1 and SP-1. By contrast, sinomenine up-regulated the expression of another transcription factor, Egr-1. These effects were restricted by mecamylamine and PNU but not by atropine. Results suggested that sinomenine can inhibit lung cancer via 7 nAChR in a negative feedback mode.

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Acetylcholine nicotinic receptor subtypes in chromaffin cells

Criado¹

2017

Pflugers Arch - Eur J Physiol

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In the adrenal gland, acetylcholine released on stimulation of the sympathetic splanchnic nerve activates neuronal-type nicotinic receptors (nAChRs) in chromaffin cells and triggers catecholamine secretion. At least two subtypes of nAChRs have been described in bovine chromaffin cells. The main subtype, a heteromeric assembly of α3, β4 and perhaps α5 subunits, is involved in the activation step of the catecholamine secretion process and is not blocked by the snake toxin α-bungarotoxin. The other is α-bungarotoxin-sensitive, and its functional role has not yet been well defined. The α7 subunit conforms the homomeric structure of this subtype. All nAChR subunits share the same molecular organization and structural data at atomic resolution level are now available for some homomeric and heteromeric ensembles. The α3, β4 and α5 subunits are clustered in genomes of different species, with the transcription factor Sp1 playing a co-ordinating role in the transcriptional regulation of these three subunits. The transcription factor Egr-1 controls the differential expression of α7 nAChR in adrenergic chromaffin cells, as happens with the enzyme phenylethanolamine N-methyl transferase. For unknown reasons, whole cell currents observed in bovine chromaffin cells clearly differ of the ones observed when different combinations of subunit RNAs are injected in oocytes. In addition to the typical nicotinic ligands, a variety of unrelated substances with clinical relevance can target nAChRs in chromaffin cells and, therefore, affect catecholamine secretion. They can act as agonists, antagonists or allosteric modulators.

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N-Benzylpiperidine Derivatives as α7 Nicotinic Receptor Antagonists

Cited by 8 publications

References 44 publications

Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors

Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors

Inhibitory effect of sinomenine on lung cancer cells via negative regulation of α7 nicotinic acetylcholine receptor

Acetylcholine nicotinic receptor subtypes in chromaffin cells

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