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.

Synthesis and muscarinic activity of 1,2,3,4-tetrahydropyrimidine derivatives.

Abstract: 3-Methyl-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde O-substituted oximes 4 and 1-(3-methyl-1,2,3,4-tetrahydropyrimidin-5-yl)ethanone O-substituted oximes 9 have been prepared as bioisosteric congeners of arecoline which is a muscarinic agonist for treatment of Alzheimer's disease. Starting from pyrimidine-5-carbaldehyde 1, formation of the 3-methylpyrimidinium salt and subsequent reduction afforded 1,2,3,4-tetrahydropyrimidine derivatives which were converted into oxalate salts in the interest of purity and stability. Binding affinities of prepared compounds for the cloned human muscarinic M1 receptor (h-M1) were determined by radioligand binding assay using [3H]-N-methylscopolamine (NMS).

Arecoline tumorigenicity in swiss strain mice on normal and vitamin B deficient diet

Abstract: Arecoline, a major alkaloid present in betel nut, was administered daily by gavage feeding to Swiss male and female mice at a dose of 1 mg/day/mouse five times a week, either alone or in combination with KNO3 or KNO3 + lime. Swiss mice of both sexes kept on a vitamin B complex-deficient diet were tested in a similar manner and compared with those receiving a normal diet. In the mice receiving a normal diet it was observed that arecoline induced tumors in 40% of males but failed to produce tumors in any of the females. Arecoline tumorigenicity in females was evident only when they received a vitamin B-deficient diet. Arecoline tumorigenicity was not evident in males when they were treated simultaneously with KNO3 + lime and kept on a normal diet. However, the same treatment administered to male mice kept on a vitamin B complex-deficient diet induced tumors in 39%.

Arecoline is cytotoxic for human endothelial cells

Abstract: Background Oral submucous fibrosis is a pre-malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial–lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors. Materials and methods Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase-contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl-thiazol-tetrazolium assay. Results Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333 μg/ml or more. Ultrastructural features of cellular stress were seen after 24-h treatment with 111 μg/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4 h with arecoline at 333 μg/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24 h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl-thiazol-tetrazolium assays. Conclusions Arecoline is cytotoxic via necrosis for endothelium, while biochemical assays indicate no appreciable cellular leakage before death and detachment, as well as no clear effect on mitochondrial function in viable cells. Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis.