Arecoline

About: Arecoline is a research topic. Over the lifetime, 744 publications have been published within this topic receiving 16015 citations. The topic is also known as: methylarecaiden & methylarecaidin.

The influence of pH on the muscarinic action of oxotremorine, arecoline, pilocarpine, and their quaternary ammonium analogs.

Abstract: Oxotremorine, arecoline, pilocarpine, and their methiodides have been assayed for muscarinic activity on isolated guinea pig ileal segments using bethanechol as a reference compound over the pH range 6.2-8.7. The relative activity of the tertiary amines decreased with increasing pH, while that of oxotremorine and arecoline methiodides was unaffected by pH. Pilocarpine methiodide was pharmacologically inert. The data were interpreted quantitatively using an iterative nonlinear regression procedure to fit an equation derived on the assumption that only the ionized forms of the compounds were active. A satisfactory fit for the five active compounds was obtained as judged by analyses of variance. The procedure also yielded estimates of the dissociation constants of the amines, which were close to those obtained by direct titration, although small significant differences were found. All three tertiary amines were more active than the corresponding quaternary ammonium compounds, and the reasons for this anomaly are discussed. Evidence is presented to indicate that pilocarpine methiodide is 1,3-dimethyl substituted on the imidazole ring, and methylation of pilocarpine therefore yields a product which is not sterically analogous to the other two methiodides.

Hypoxia inducible factor-1α expression in areca quid chewing-associated oral squamous cell carcinomas.

Abstract: Oral Diseases (2010) 16, 696–701 Objectives: Hypoxia inducible factor (HIF)-1α gene expression is mainly induced by tissue hypoxia. Overexpression of HIF-1α has been demonstrated in a variety of cancers. The aim of this study was to compare HIF-1α expression in normal human oral epithelium and areca quid chewing-associated oral squamous cell carcinoma (OSCC) and further to explore the potential mechanisms that may lead to induce HIF-1α expression. Methods: Twenty-five OSCC from areca quid chewing-associated OSCC and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N-acetyl-l-cysteine (NAC), AP-1 inhibitor curcumin, extracellular signal-regulated protein kinase inhibitor PD98059, and protein kinase C inhibitor staurosporine were added to find the possible regulatory mechanisms. Results: Hypoxia inducible factor-1α expression was significantly higher in OSCC specimens than normal specimen (P < 0.05). Arecoline was found to elevate HIF-1α expression in a dose- and time-dependent manner (P < 0.05). The addition of NAC, curcumin, PD98059, and staurosporine markedly inhibited the arecoline-induced HIF-1α expression (P < 0.05). Conclusions: Hypoxia inducible factor-1α expression is significantly upregulated in areca quid chewing-associated OSCC and HIF-1α expression induced by arecoline is downregulated by NAC, curcumin, PD98059, and staurosporine.

M1 receptor activation is a requirement for arecoline analgesia

Abstract: Arecoline. a drug obtained from the Areca Catechu L., induced a dose-dependent antinociception (0.3-1 mg kg(-1) i.p.) which was prevented by the muscarinic antagonists pirenzepine (0.1 microg per mouse i.c.v.) and S-(-)-ET-126 (0.01 microg per mouse i.c.v.). A dose-dependent inhibition of the antinociception induced by arecoline was observed after inactivation of the M1 gene by an antisense oligodeoxyribonucleotide (aODN). This effect was detected 24 h after the last i.c.v. injection of aODN. These results indicate that arecoline antinociception is mediated by the activation of central M1 muscarinic receptors.

Effects of acute and chronic arecoline in adult zebrafish: Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia

Abstract: Arecoline is a naturally occurring psychoactive alkaloid with partial agonism at nicotinic and muscarinic acetylcholine receptors. Arecoline consumption is widespread, making it the fourth (after alcohol, nicotine and caffeine) most used substance by humans. However, the mechanisms of acute and chronic action of arecoline in-vivo remain poorly understood. Animal models are a valuable tool for CNS disease modeling and drug screening. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a promising novel model organism for neuroscience research. Here, we assessed the effects of acute and chronic arecoline on adult zebrafish behavior and physiology. Overall, acute and chronic arecoline treatments produced overt anxiolytic-like behavior (without affecting general locomotor activity and whole-body cortisol levels), with similar effects also caused by areca nut water extracts. Acute arecoline at 10 mg/L disrupted shoaling, increased social preference, elevated brain norepinephrine and serotonin levels and reduced serotonin turnover. Acute arecoline also upregulated early protooncogenes c-fos and c-jun in the brain, whereas chronic treatment with 1 mg/L elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). Finally, acute 2-h discontinuation of chronic arecoline treatment evoked withdrawal-like anxiogenic behavior in zebrafish. In general, these findings support high sensitivity of zebrafish screens to arecoline and related compounds, and reinforce the growing utility of zebrafish for probing molecular mechanisms of CNS drugs. Our study also suggests that novel anxiolytic drugs can eventually be developed based on arecoline-like molecules, whose integrative mechanisms of CNS action may involve monoaminergic and neuro-immune modulation.