Dequalinium chloride is an antagonists of α7 nicotinic acetylcholine receptors

Belanger-Coast, Matthieu Gibson; Zhang, Mei; Bugay, Vladislav; Gutierrez, Raul A.; Gregory, Summer R.; Yu, Weifeng; Brenner, Robert

doi:10.1016/j.ejphar.2022.175000

Cited by 4 publications

(2 citation statements)

References 51 publications

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“…These anticancer effects are mediated by antagonizing α7 nAChR, in addition to its antimitochondrial activity. 104 A multivalent ligand of nicotine was also developed as an α7 nAChR antagonist. Divalent and heptavalent nicotine deriva- tives with varying ethylene glycol lengths and cyclodextrin cores were synthesized and evaluated for antagonist properties.…”

Section: ■ the Development Of α7 Nicotinic Acetylcholine Receptor Ant...mentioning

confidence: 99%

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Targeting Alpha7 Nicotinic Acetylcholine Receptors in Lung Cancer: Insights, Challenges, and Therapeutic Strategies

Arunrungvichian,

Vajragupta,

Hayakawa

et al. 2023

ACS Pharmacol. Transl. Sci.

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Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is an ion-gated calcium channel that plays a significant role in various aspects of cancer pathogenesis, particularly in lung cancer. Preclinical studies have elucidated the molecular mechanism underlying α7 nAChR-associated lung cancer proliferation, chemotherapy resistance, and metastasis. Understanding and targeting this mechanism are crucial for developing therapeutic interventions aimed at disrupting α7 nAChR-mediated cancer progression and improving treatment outcomes. Drug research and discovery have determined natural compounds and synthesized chemical antagonists that specifically target α7 nAChR. However, approved α7 nAChR antagonists for clinical use are lacking, primarily due to challenges related to achieving the desired selectivity, efficacy, and safety profiles required for effective therapeutic intervention. This comprehensive review provided insights into the molecular mechanisms associated with α7 nAChR and its role in cancer progression, particularly in lung cancer. Furthermore, it presents an update on recent evidence about α7 nAChR antagonists and addresses the challenges encountered in drug research and discovery in this field.

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Section: ■ the Development Of α7 Nicotinic Acetylcholine Receptor Ant...mentioning

confidence: 99%

“…The anticancer effect of dequalinium chloride was studied in glioma cells and promyelocytic leukemia, where it exhibited growth inhibition and induced apoptosis. These anticancer effects are mediated by antagonizing α7 nAChR, in addition to its antimitochondrial activity …”

Section: The Development Of α7 Nicotinic Acetylcholine Receptor Antag...mentioning

confidence: 99%

Targeting Alpha7 Nicotinic Acetylcholine Receptors in Lung Cancer: Insights, Challenges, and Therapeutic Strategies

Arunrungvichian,

Vajragupta,

Hayakawa

et al. 2023

ACS Pharmacol. Transl. Sci.

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Central nervous system disturbances by thiamethoxam in Japanese quail (Coturnix japonica): In vivo, ex vivo, and in silico study

Pan,

Niu,

et al. 2024

Environmental Pollution

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Berberine and palmatine, acting as allosteric potential ligands of α7 nAChR, synergistically regulate inflammation and phagocytosis of microglial cells

Xia,

Wang,

Lin

et al. 2024

The FASEB Journal

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Berberine and palmatine are isoquinoline quaternary alkaloids derived from Chinese medicinal herbs. These alkaloids have shown promising synergy in inhibiting acetylcholinesterase (AChE), indicating their potential in treating Alzheimer's disease (AD). Besides, the anti‐inflammatory effects of berberine and palmatine have been widely reported, although the underlying mechanism remains unclear. Here, we found that berberine and palmatine could induce calcium ion (Ca2+) influx via activating α7 nicotinic acetylcholine receptor (α7 nAChR) in cultured microglial cells, possibly serving as its allosteric potential ligands. Furthermore, we examined the synergistic anti‐inflammatory effects of berberine and palmatine in the LPS‐induced microglia, that significantly suppressed the production of TNF‐α and iNOS. Notably, this suppression was reversed by co‐treatment with a selective antagonist of α7 nAChR. Moreover, the alkaloid‐induced microglial phagocytosis was shown to be mediated by the induction of Ca2+ influx through α7 nAChR and subsequent CaMKII‐Rac1‐dependent pathway. Additionally, the combination of berberine and palmatine, at low concentration, protected against the LPS‐induced endoplasmic reticulum stress and mitochondrial dysfunction in microglia. These findings indicate the potential of berberine and palmatine, either individually or in combination, in contributing to anti‐AD drug development, which provide valuable insights into the mechanisms by which natural products, such as plant alkaloids, exert their anti‐AD effects.

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Dequalinium chloride is an antagonists of α7 nicotinic acetylcholine receptors

Cited by 4 publications

References 51 publications

Targeting Alpha7 Nicotinic Acetylcholine Receptors in Lung Cancer: Insights, Challenges, and Therapeutic Strategies

Targeting Alpha7 Nicotinic Acetylcholine Receptors in Lung Cancer: Insights, Challenges, and Therapeutic Strategies

Central nervous system disturbances by thiamethoxam in Japanese quail (Coturnix japonica): In vivo, ex vivo, and in silico study

Berberine and palmatine, acting as allosteric potential ligands of α7 nAChR, synergistically regulate inflammation and phagocytosis of microglial cells

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