Arecoline

Arecoline

Systematic (IUPAC) name
Methyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate
Clinical data
Legal status	Uncontrolled
Identifiers
CAS Number	63-75-2 Y
ATC code	none
PubChem	CID: 2230
IUPHAR/BPS	296
DrugBank	DB04365 Y
ChemSpider	13872064 Y
UNII	4ALN5933BH Y
KEGG	C10129 Y
ChEBI	CHEBI:2814 N
ChEMBL	CHEMBL7303 Y
Chemical data
Formula	C8H13NO2
Molecular mass	155.194 g/mol
SMILES O=C(OC)C=1CN(C)CCC=1
InChI InChI=1S/C8H13NO2/c1-9-5-3-4-7(6-9)8(10)11-2/h4H,3,5-6H2,1-2H3 Y Key:HJJPJSXJAXAIPN-UHFFFAOYSA-N Y
Physical data
Density	1.0495 g/cm3
Boiling point	209 °C (408 °F)
NY (what is this?)  (verify)

Arecoline (/əˈrɛkəliːn/) is a nicotinic acid-based alkaloid found in the areca nut, the fruit of the areca palm (Areca catechu). It is an odourless oily liquid.

Chemistry

Arecoline is a base, and its conjugate acid has a pK_a ~ 6.8. Arecoline is volatile in steam, miscible with most organic solvents and water, but extractable from water by ether in presence of dissolved salts. Being basic, arecoline forms salts with acids. The salts are crystalline, but usually deliquescent: the hydrochloride, arecoline•HCl, forms needles, m.p. 158 °C; the hydrobromide, arecoline•HBr, forms slender prisms, mp. 177-179 °C from hot alcohol; the aurichloride, arecoline•HAuCl₄, is an oil, but the platinichloride, arecoline₂•H₂PtCl₆, mp. 176 °C, crystallizes from water in orange-red rhombohedrons. The methiodide forms glancing prisms, mp. 173-174 °C.

Biological action

In many Asian cultures, the areca nut is chewed along with betel leaf to obtain a stimulating effect. Arecoline 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.).

LD₅₀: 100 mg/kg, administered subcutaneously in mouse.

Current science is confident that areca nut chewing is carcinogenic. Current science thinks that that effect is probably at least partly because of arecoline itself, although it could also be from the other constituents of the nut as well, some of which are precursors to nitrosamines that form in the mouth during chewing. Section 5.5 Evaluation on page 238 of IARC Monograph 85-6 states the following:

• [...]
• There is sufficient evidence in humans for the carcinogenicity of betel quid without tobacco. Betel quid without tobacco causes oral cancer.
• There is sufficient evidence in experimental animals for the carcinogenicity of betel quid without tobacco.
• There is sufficient evidence in experimental animals for the carcinogenicity of betel quid with tobacco.
• There is sufficient evidence in experimental animals for the carcinogenicity of areca nut.
• There is sufficient evidence in experimental animals for the carcinogenicity of areca nut with tobacco.
• There is limited evidence in experimental animals for the carcinogenicity of arecoline.
• There is inadequate evidence in experimental animals for the carcinogenicity of arecaidine.
• [...]

Uses

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 intravenously 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 also been used medicinally as an antihelmintic (a drug against parasitic worms).