ARECOLINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H13NO2
Molecular Weight	155.1943
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(=O)C1=CCCN(C)C1

InChI

InChIKey=HJJPJSXJAXAIPN-UHFFFAOYSA-N

InChI=1S/C8H13NO2/c1-9-5-3-4-7(6-9)8(10)11-2/h4H,3,5-6H2,1-2H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30951892 | https://www.ncbi.nlm.nih.gov/pubmed/30925742 | https://www.ncbi.nlm.nih.gov/pubmed/11482763

Arecoline is a natural alkaloid and is an effective constituent of Areca catechu L. (Arecaceae) with various pharmacological activities including effects on nervous, cardiovascular, digestive and endocrine systems and anti-parasitic effects. Antinociception of arecoline is mediated by the activation of the muscarinic acetylcholine receptors. It was found that this compound leads to oral submucosal fibrosis and oral cancer. Lung cancer is a severe type of carcinoma with high cell motility that is difficult to treat. As a result, further studies are needed to reduce or eliminate the toxicity of the compound before developing into a new drug.

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19767446	Agonist 2678	7.0 nM [EC50]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19168056	Agonist 2678	95.0 nM [EC50]
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19168056	Agonist 2678	11.0 nM [EC50]
Muscarinic acetylcholine receptor M4 86 Target ID: CHEMBL1821 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19168056	Agonist 2678	0.41 µM [EC50]
Muscarinic acetylcholine receptor M5 62 Target ID: CHEMBL2035 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19168056	Agonist 2678	69.0 nM [EC50]
Muscarinic acetylcholine receptor 160 Target ID: CHEMBL2094109 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7783150 \| https://www.ncbi.nlm.nih.gov/pubmed/10857465 \| https://adisinsight.springer.com/drugs/800014145	Agonist 2678	73.0 nM [EC50]

PubMed

Title	Date	PubMed
[Proceedings: On the central action of nomifensine (author's transl)].	1976	989390
Effect of muscarinic cholinergic drugs on morphine-induced catalepsy, antinociception and changes in brain dopamine metabolism.	1977 Mar 23	403561
Evidence that a nigral gabaergic--cholinergic balance controls posture.	1979 Jan 1	569589
Anti-tremor action of C10Dichol, a peripheral acetylcholine synthesis inhibitor.	1980	6258692
Modification of cholinergic tremor by apomorphine and L-dopa in rats.	1980 Nov-Dec	7246199
[Modification, by lithium, of catalepsy induced by central cholinergic stimulants and morphine-like drugs].	1981	6268258
Physostigmine and arecoline: effects of intravenous infusions in Alzheimer presenile dementia.	1981 Jan	7023592
The effects of organophosphate-induced cholinergic stimulation on the antibody response to sheep erythrocytes in inbred mice.	1983 Apr	6857660
Neuropharmacology of the parasitic trematode, Schistosoma mansoni.	1983 Jan	6130710
Effects of dopamine agonists, catecholamine depletors, and cholinergic and GABAergic drugs on acute dyskinesias in squirrel monkeys.	1984	6320248
Screening for new compounds with antiherpes activity.	1984 Oct	6517562
Subclassification of muscarinic receptors in the heart, urinary bladder and sympathetic ganglia in the pithed rat. Selectivity of some classical agonists.	1985 Dec	4094621
Ethanol withdrawal tremor does not interact with physostigmine-induced tremor in rat.	1985 Sep	4048228
Status epilepticus is produced by administration of cholinergic agonists to lithium-treated rats: comparison with kainic acid.	1987 Dec	2824229
Effects of nootropic drugs in a scopolamine-induced amnesia model in mice.	1988	3137602
Alleviation of scopolamine amnesia by different retrieval enhancing treatments.	1988 Aug	3227033
Amelioration of experimental amnesia (passive avoidance failure) in rodents by the selective M1 agonist AF102B.	1988 Dec	3244205
[Nonuniform expression of the dopamine-positive effect in different central m-cholinergic blockaders].	1988 Mar-Apr	3378602
Pharmacological characterization of the M1 muscarinic receptors expressed in murine fibroblast B82 cells.	1989 Feb	2537406
Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384) on learning and memory in rats.	1989 May	2724699
Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.	1991 Jan-Feb	1710653
[The possible role of presynaptic effects in realizing the protective action of M-cholinolytics in dimethyl dichlorovinyl phosphate poisoning].	1991 Jul-Aug	1664807
Intrathecal cholinergic agonists lessen bupivacaine spinal-block-induced hypotension in rats.	1994 Jul	8010419
[The selectivity of the action of muscarinic agonists in vivo].	1994 Mar-Apr	8205054
Pharmacological activity and receptor-binding characteristics of 2 beta-(2'-phenyl-2'-cyclopentyl-2'-hydroxy-ethoxy)tropane and its optical isomers.	1996 Mar-Apr	8937624
Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.	1997 Jul	9224827
Anticholinergic activity in mice and receptor-binding properties in rats of a series of synthetic tropane derivatives.	1997 Mar	9231353
Anti-nicotinic properties of anticholinergic antiparkinson drugs.	1998 Nov	9877318
Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor.	2000 Mar 31	10857465
M1 receptor activation is a requirement for arecoline analgesia.	2001 May-Jul	11482763
High-performance liquid chromatographic determination of arecoline in human saliva.	2004 Apr 2	15065782
Arecoline excites the colonic smooth muscle motility via M3 receptor in rabbits.	2004 Jun 30	15481791
Oral submucous fibrosis: review on aetiology and pathogenesis.	2006 Jul	16311067
Arecoline inhibits the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1A1 activation in human hepatoma cells.	2007 Jul 19	17234337
Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling.	2007 Nov	17682004
Differential effect of arecoline on the endogenous dioxin-responsive cytochrome P450 1A1 and on a stably transfected dioxin-responsive element-driven reporter in human hepatoma cells.	2007 Oct 1	17707585
Synthesis of Novel 3-Aryl-N-Methyl-1,2,5,6-Tetrahydropyridine Derivatives by Suzuki coupling: As Acetyl Cholinesterase Inhibitors.	2007 Sep 5	19662135
The upregulation of metallothionein-1 expression in areca quid chewing-associated oral squamous cell carcinomas.	2008 Feb	17418620
[The characterization of central neuromediation in rats fed with magnesium-deprived diet before and after magnesium replenishment].	2008 Jul	18767395
Co-treating with arecoline and 4-nitroquinoline 1-oxide to establish a mouse model mimicking oral tumorigenesis.	2010 Jan 5	19840781
Effects of arecoline on adipogenesis, lipolysis, and glucose uptake of adipocytes-A possible role of betel-quid chewing in metabolic syndrome.	2010 Jun 15	20406654
Interaction of phytochemicals with hypoglycemic drugs on glucose uptake in L6 myotubes.	2011 Feb 15	20724125
Bronchial epithelium-derived IL-8 and RANTES increased bronchial smooth muscle cell migration and proliferation by Krüppel-like factor 5 in areca nut-mediated airway remodeling.	2011 May	21297082
Areca nut induces miR-23a and inhibits repair of DNA double-strand breaks by targeting FANCG.	2011 Oct	21750350
Arecoline augments cellular proliferation in the prostate gland of male Wistar rats.	2011 Sep 1	21741983
Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells.	2012 Jan 15	22108589
Arecoline inhibits and destabilizes agrin-induced acetylcholine receptor cluster formation in C2C12 myotubes.	2013 Oct	23933062
Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress.	2014 Aug	25056785
Helioxanthin suppresses the cross talk of COX-2/PGE2 and EGFR/ERK pathway to inhibit Arecoline-induced Oral Cancer Cell (T28) proliferation and blocks tumor growth in xenografted nude mice.	2016 Dec	26464283
Role of autophagy induced by arecoline in angiogenesis of oral submucous fibrosis.	2019 Jun	30951892

Patents

Sample Use Guides

In Vitro Use Guide

different concentrations of Arecoline treatment (10 µM, 20 µM, and 40 µM) significantly increased the cell migration ability in A549 and CL1-0 cells and promoted the formation of the filamentous actin (F-actin) cytoskeleton, which is a crucial element for cell migration.

Name

Type

Language

ARECOLINE

Common Name

English

NSC-56321

Code

English

ARECOLINE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47796