Arecoline
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Basic Info
| Common Name | Arecoline(F05485) |
| 2D Structure | |
| Description | Arecoline 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 (A7876, A7878, A7879). 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. |
| FRCD ID | F05485 |
| CAS Number | 63-75-2 |
| PubChem CID | 2230 |
| Formula | C8H13NO2 |
| IUPAC Name | methyl 1-methyl-3,6-dihydro-2H-pyridine-5-carboxylate |
| InChI Key | HJJPJSXJAXAIPN-UHFFFAOYSA-N |
| InChI | InChI=1S/C8H13NO2/c1-9-5-3-4-7(6-9)8(10)11-2/h4H,3,5-6H2,1-2H3 |
| Canonical SMILES | CN1CCC=C(C1)C(=O)OC |
| Isomeric SMILES | CN1CCC=C(C1)C(=O)OC |
| Wikipedia | Arecoline |
| Synonyms |
Arecoline base
arecoline
Arecaline
Arecholine
Methylarecaiden
Methylarecaidin
Arecolin
63-75-2
Arekolin
Arecaidine methyl ester
|
| Classifies |
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Alkaloids and derivatives |
| Class | Not available |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Alkaloids and derivatives |
| Alternative Parents | |
| Molecular Framework | Aliphatic heteromonocyclic compounds |
| 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 |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 155.197 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 2 |
| Complexity | 187 |
| Monoisotopic Mass | 155.095 |
| Exact Mass | 155.095 |
| XLogP | 0.3 |
| Formal Charge | 0 |
| Heavy Atom Count | 11 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9613 |
| Human Intestinal Absorption | HIA+ | 0.9713 |
| Caco-2 Permeability | Caco2+ | 0.6557 |
| P-glycoprotein Substrate | Substrate | 0.6628 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.6202 |
| Non-inhibitor | 0.9697 | |
| Renal Organic Cation Transporter | Inhibitor | 0.6075 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5352 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8958 |
| CYP450 2D6 Substrate | Substrate | 0.5321 |
| CYP450 3A4 Substrate | Substrate | 0.5051 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9045 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9230 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9061 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9820 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9564 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Strong inhibitor | 0.5396 |
| Non-inhibitor | 0.8535 | |
| AMES Toxicity | AMES toxic | 0.9107 |
| Carcinogens | Non-carcinogens | 0.8927 |
| Fish Toxicity | High FHMT | 0.5886 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.6183 |
| Honey Bee Toxicity | Low HBT | 0.5409 |
| Biodegradation | Ready biodegradable | 0.9234 |
| Acute Oral Toxicity | III | 0.7876 |
| Carcinogenicity (Three-class) | Non-required | 0.6491 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | 0.7474 | LogS |
| Caco-2 Permeability | 1.1705 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.8241 | LD50, mol/kg |
| Fish Toxicity | 1.5872 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.1315 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Arecoline aggravates hypothyroidism in metabolic stress in mice. | Arch Physiol Biochem | 2017 May | 28019102 |
| Epithelial atrophy in oral submucous fibrosis is mediated by copper (II) andarecoline of areca nut. | J Cell Mol Med | 2015 Oct | 26248978 |
| Areca nut-induced buccal mucosa fibroblast contraction and its signaling: apotential role in oral submucous fibrosis--a precancer condition. | Carcinogenesis | 2013 May | 23349021 |
| Separation of polyphenols and arecoline from areca nut (Areca catechu L.) by solvent extraction, its antioxidant activity, and identification of polyphenols. | J Sci Food Agric | 2013 Aug 15 | 23494978 |
| New biological properties of coffee melanoidins. | Food Funct | 2013 Aug | 23712216 |
| Activation of TGF-β pathway by areca nut constituents: a possible cause of oral submucous fibrosis. | PLoS One | 2012 | 23284772 |
| Areca nut extracts enhance the development of CD11b(+) Gr-1(+) cells with thecharacteristics of myeloid-derived suppressor cells in antigen-stimulated mice. | J Oral Pathol Med | 2011 Nov | 21481006 |
| A preliminary report on the toxicity of arecoline on early pregnancy in mice. | Food Chem Toxicol | 2011 Jan | 20940028 |
| Effect of magnesium chloride on psychomotor activity, emotional status, and acutebehavioural responses to clonidine, d-amphetamine, arecoline, nicotine,apomorphine, and L-5-hydroxytryptophan. | Nutr Neurosci | 2011 Jan | 21535917 |
| Arecoline N-oxide: its mutagenicity and possible role as ultimate carcinogen inareca oral carcinogenesis. | J Agric Food Chem | 2011 Apr 13 | 21370913 |
| Xenobiotic metabolism: a view through the metabolometer. | Chem Res Toxicol | 2010 May 17 | 20232918 |
| Effects of arecoline on adipogenesis, lipolysis, and glucose uptake ofadipocytes-A possible role of betel-quid chewing in metabolic syndrome. | Toxicol Appl Pharmacol | 2010 Jun 15 | 20406654 |
| Features of central neurotransmission in animals in conditions of dietarymagnesium deficiency and after its correction. | Neurosci Behav Physiol | 2009 Sep | 19621270 |
| Availability and characteristics of betel products in the U.S. | J Psychoactive Drugs | 2008 Sep | 19004423 |
| Areca nut extracts reduce the intracellular reactive oxygen species and release of myeloperoxidase by human polymorphonuclear leukocytes. | J Periodontal Res | 2007 Feb | 17214642 |
| Oral submucous fibrosis: review on aetiology and pathogenesis. | Oral Oncol | 2006 Jul | 16311067 |
| [Studies on the effect-increasing components for molluscacides in nut of Arecacatech L]. | Zhongguo Zhong Yao Za Zhi | 2000 Mar | 12212099 |
| [Studies on the increasing-effect components for molluscicides in nut of Arecacatech]. | Zhong Yao Cai | 1999 Nov | 12571896 |
| Lead-induced changes in muscarinic cholinergic sensitivity. | Neurotoxicology | 1995 Summer | 7566693 |
| Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cellsin vitro. | Int J Cancer | 1991 Feb 1 | 1993547 |
Targets
- 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
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- 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