You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2014-09-11 02:04:24 UTC
Update Date2014-12-24 20:26:54 UTC
Accession NumberT3D4675
Identification
Common NameArecoline
ClassSmall Molecule
DescriptionArecoline is found in nuts. Arecoline is isolated from betel nuts Arecoline is an alkaloid natural product found in the areca nut, the fruit of the areca palm (Areca catechu). It is an oily liquid that is soluble in water, alcohols, and ether. Owing to its muscarinic and nicotinic agonist properties, arecoline has shown improvement in the learning ability of healthy volunteers. Since one of the hallmarks of Alzheimer's disease is a cognitive decline, arecoline was suggested as a treatment to slow down this process and arecoline administered via i.v. route did indeed show modest verbal and spatial memory improvement in Alzheimer's patients, though due to arecoline's possible carcinogenic properties, it is not the first drug of choice for this degenerative disease. Arecoline has been shown to exhibit apoptotic, excitant and steroidogenic functions (1, 2, 3). Arecoline belongs to the family of Alkaloids and Derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.
Compound Type
  • Amine
  • Ester
  • Ether
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Nootropic Agent
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
1,2,5,6-Tetrahydro-1-methylnicotinic acid, methyl ester
Arecaidine methyl ester
Arecaline
Arecholin
Arecholine
Arecolin
Arecoline base
Arecoline hydrobromide
Arekolin
Methyl 1,2,5, 6-tetrahydro-1-methylnicotinate
Methyl 1,2,5,6-tetrahydro-1-methylnicotinate
Methyl 1-methyl-1,2,5,6-tetrahydro-3-pyridinecarboxylate
Methyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate
Methyl 1-methyl-5,6-dihydro-2H-pyridine-3-carboxylate
Methyl N-methyl-1,2,5, 6-tetrahydronicotinate
Methyl N-methyl-1,2,5,6-tetrahydronicotinate
Methyl N-methyltetrahydronicotinate
Methylarecaiden
Methylarecaidin
N-Methyl-beta -carboxylic acid methyl ester
N-Methyltetrahydronicotinic acid, methyl ester
Nicotinic acid, 1,2,5,6-tetrahydro-1-methyl-, methyl ester
Chemical FormulaC8H13NO2
Average Molecular Mass155.194 g/mol
Monoisotopic Mass155.095 g/mol
CAS Registry Number63-75-2
IUPAC Namemethyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate
Traditional Namearecoline
SMILESCOC(=O)C1=CCCN(C)C1
InChI IdentifierInChI=1S/C8H13NO2/c1-9-5-3-4-7(6-9)8(10)11-2/h4H,3,5-6H2,1-2H3
InChI KeyInChIKey=HJJPJSXJAXAIPN-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alkaloids and derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassNot Available
Sub ClassNot Available
Direct ParentAlkaloids and derivatives
Alternative Parents
Substituents
  • Alkaloid or derivatives
  • Hydropyridine
  • Methyl ester
  • Enoate ester
  • Alpha,beta-unsaturated carboxylic ester
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Tertiary amine
  • Tertiary aliphatic amine
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Organoheterocyclic compound
  • Azacycle
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Organic oxide
  • Hydrocarbon derivative
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceOdourless oily liquid.
Experimental Properties
PropertyValue
Melting Point< 25°C
Boiling Point209°C
Solubility1E+006 mg/L (at 25°C)
LogP0.35
Predicted Properties
PropertyValueSource
Water Solubility446.0 mg/mLALOGPS
logP0.55ALOGPS
logP0.65ChemAxon
logS0.46ALOGPS
pKa (Strongest Basic)8.23ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area29.54 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity43.86 m3·mol-1ChemAxon
Polarizability17.1 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-006w-9400000000-98b26a9d2867d710059eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0900000000-13bcb3825f7244e9bfd3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05fr-5900000000-4c54ca467a6647c61870View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00rw-9000000000-ff7785df405dc6c7b136View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0900000000-1de11420c61028c65308View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-1900000000-ff4ff3298d65bc8e1a2bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05fu-9300000000-f368ae9f151a5d63114cView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0006-9400000000-c2ac70d939302e3f979bView in MoNA
Toxicity Profile
Route of ExposureIngestion
Mechanism of ToxicityArecoline is the primary active ingredient responsible for the central nervous system effects of the areca nut. Arecoline has been compared to nicotine; however, nicotine acts primarily on the nicotinic acetylcholine receptor. Arecoline is known to be a partial agonist of muscarinic acetylcholine M1, M2, M3 receptors and M4, which is believed to be the primary cause of its parasympathetic effects (such as pupillary constriction, bronchial constriction, etc.). (Wikipedia) Arecoline is cytotoxic to human gingival fibroblasts at a concentration higher than 50 μg/ml by depleting intracellular thiols and inhibiting mitochondrial activity (P<0.05). In addition, the cells displayed a marked arrest at G2/M phase in a dose-dependent manner. (4)
MetabolismNot Available
Toxicity ValuesLD50: 100 mg/kg, administered subcutaneously in mouse (Wikipedia)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesArecoline is found in nuts. Arecoline is isolated from betel nuts Arecoline is an alkaloid natural product found in the areca nut, the fruit of the areca palm (Areca catechu). Since one of the hallmarks of Alzheimer's disease is a cognitive decline, arecoline was suggested as a treatment to slow down this process and arecoline administered via i.v. Arecoline has also been used medicinally as an antihelmintic (a drug against parasitic worms).
Minimum Risk LevelNot Available
Health EffectsPupillary constriction, bronchial constriction.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB04365
HMDB IDHMDB30353
PubChem Compound ID2230
ChEMBL IDNot Available
ChemSpider ID13872064
KEGG IDC10129
UniProt IDNot Available
OMIM ID
ChEBI ID101022
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkArecoline
References
Synthesis Reference

K. S. Keshave Murthy, Allan W. Rey, Dan S. Matu, “Preparation of 1,2,5,6-tetra-hydro-3-carboalkoxypridines such as arecoline and salts of 1,2,5,6-tetrahydro-3-carboalkoxypridines and arecoline hydrobromide.” U.S. Patent US6132286, issued October 17, 2000.

MSDST3D4675.pdf
General References
  1. Shih YT, Chen PS, Wu CH, Tseng YT, Wu YC, Lo YC: Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system. Free Radic Biol Med. 2010 Nov 30;49(10):1471-9. doi: 10.1016/j.freeradbiomed.2010.07.017. Epub 2010 Aug 4. [20691257 ]
  2. Yang YR, Chang KC, Chen CL, Chiu TH: Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor. Chin J Physiol. 2000 Mar 31;43(1):23-8. [10857465 ]
  3. Wang SW, Hwang GS, Chen TJ, Wang PS: Effects of arecoline on testosterone release in rats. Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E497-504. doi: 10.1152/ajpendo.00045.2008. Epub 2008 Jun 17. [18559981 ]
  4. Chang YC, Hu CC, Lii CK, Tai KW, Yang SH, Chou MY: Cytotoxicity and arecoline mechanisms in human gingival fibroblasts in vitro. Clin Oral Investig. 2001 Mar;5(1):51-6. [11355099 ]
  5. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da