Plate 254 of 545Verified

Arecoline

Also known asArecolin · Arecaline · Arecholine · Methylarecaiden · Methylarecaidin · Arekolin · Arecoline base · Arecaidine methyl ester

methyl 1-methyl-3,6-dihydro-2H-pyridine-5-carboxylate

PubChem CID: 2230
ChEMBL: CHEMBL7303
Measurements: 57
InChIKey: HJJPJSXJAXAIPN-UHFFFAOYSA-N

I · Summary

What is known

Published passages, each quoted whole and attributed to the database that published it. Two blocks are written here rather than quoted, and both say so where they stand: the synthesized summary at the top, which may draw only on the passages beneath it, and the history note, which cites the works it came from. Every claim in either carries a marker to its source.

What it is

Arecoline is a tetrahydropyridine that is 1,2,5,6-tetrahydropyridine with a methyl group at position 1, and a methoxycarbonyl group at position 3. An alkaloid found in the areca nut, it acts as an agonist of muscarinic acetylcholine. It has a role as a metabolite and a muscarinic agonist. It is a methyl ester, a pyridine alkaloid, a tetrahydropyridine and an enoate ester.
ChEBI
An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetylcholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands.
DrugBank
arecoline has been reported in Eremophila fraseri with data available.
LOTUS - the natural products occurrence database
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 prop…
Toxin and Toxin Target Database (T3DB)

Recognized use

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). 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).
Toxin and Toxin Target Database (T3DB)

History, discovery and cultural use

— Not in this archive. PubChem, ChEMBL and the Human Protein Atlas publish pharmacology, regulation and toxicology, and none of them publishes a heading for when Arecoline was first made, by whom, or how it has been used. That is a gap in the databases this site reads and not a gap in the literature — the history of these compounds is written, at length and under peer review, in the works below. This site does not summarize them; it says where they are. Where a published passage above happens to touch origin or traditional use, it appears inside the entry that carries it.

Histories of this field

Scholarship on psychedelics generally, not on Arecoline specifically. Whether any of these treats this compound is a question for the book, not for this page.

Mescaline: A Global History of the First Psychedelic
Traces mescaline and the peyote and San Pedro cacti from pre-Columbian ritual use through nineteenth-century chemistry to twentieth-century psychiatry and the counterculture.
Jay M. Mescaline: A Global History of the First Psychedelic. Yale University Press, New Haven and London; 2019. ISBN 9780300231076.
Expanding Mindscapes: A Global History of Psychedelicsopen access
Essays on the international and cross-cultural history of psychedelic science, deliberately decentring the standard North American and European account.
Dyck E, Elcock C, editors. Expanding Mindscapes: A Global History of Psychedelics. The MIT Press, Cambridge MA; 2023. ISBN 9780262546935 (paper), 9780262376891 (open access). doi:10.7551/mitpress/14417.001.0001.
Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers
Botany, ethnography and chemistry of the principal hallucinogenic plants, by the founder of modern ethnobotany and the chemist who first synthesized LSD.
Schultes RE, Hofmann A, Rätsch C. Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers. 2nd ed. Healing Arts Press, Rochester VT; 2001. ISBN 9780892819799.
Psychonauts: Drugs and the Making of the Modern Mind
The tradition of scientific self-experimentation with psychoactive drugs, and its part in the emergence of psychology and of modernism.
Jay M. Psychonauts: Drugs and the Making of the Modern Mind. Yale University Press, New Haven; 2023. ISBN 9780300257946.
Ancient Psychoactive Substances
Archaeological and bioarchaeological evidence for psychoactive plant use across the ancient world.
Fitzpatrick SM, editor. Ancient Psychoactive Substances. University Press of Florida, Gainesville; 2018. ISBN 9780813056708.
History and Current Status of Psychedelics and Entactogens for the Treatment of Psychiatric Disorders
A chapter tracing psychedelic and entactogen research from earlier ritual use through the mid-century research period to current clinical trials.
Stroud C, Posey Norris SM, Matney C, editors. History and Current Status of Psychedelics and Entactogens for the Treatment of Psychiatric Disorders. In: Exploring Psychedelics and Entactogens as Treatments for Psychiatric Disorders: Proceedings of a Workshop. National Academies Press, Washington DC; 2022. NBK587225.
Workshop proceedings record what participants said; they are not a consensus statement of the National Academies.
Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions
Peer-reviewed review covering the isolation, synthesis, pharmacology and ritual use of peyote and mescaline.
Dinis-Oliveira RJ, Pereira CL, da Silva DD. Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions. Current Molecular Pharmacology 12(3):184–194; 2019. doi:10.2174/1874467211666181010154139.

Institutional archives

Heffter Research Institute Funds and coordinates clinical research on psilocybin, and keeps records of the studies it has supported since 1993. Sponsors the research it archives.
Multidisciplinary Association for Psychedelic Studies (MAPS) Sponsors clinical research, chiefly on MDMA-assisted therapy, and publishes an archive of historical and contemporary documents. A sponsor and an advocacy organization, not a disinterested archive; its clinical programme has a commercial arm.

The rest of this dossier

Affinity — 57 measurements in this archive, equilibrium constants kept apart from functional readouts.
Toxicology — 1 published passage, plus any assay in this archive bearing on toxicity.
Legal — no DEA record is held here — which is not a finding that this compound is uncontrolled.

Passages via PubChem descriptive sections, aggregating DrugBank, LiverTox, FDA, DEA, HSDB, EPA. Each is quoted whole and attributed to the database that published it. The only prose written here about Arecoline is the history note, which says so on its face and carries a reference for every claim in it.

II · Identity

Structure and descriptors

Descriptors are computed here with RDKit from the structure PubChem returns — not from the archive's stored copy, so an edited local structure cannot reach this table.

2D structural depiction of Arecoline — Depiction served by PubChem for CID 2230. Not redrawn here, so the picture and the identity come from the same record.

Formula: C8H13NO2R
Molecular weight: 155.20g/molR
Exact mass: 155.0946DaR
cLogP: 0.42R
TPSA: 29.5Å²R
H-bond donors: 0R
H-bond acceptors: 3R
Rotatable bonds: 1R
Aromatic rings: 0R
Heavy atoms: 11R
Fraction sp³: 0.625R
Formal charge: 0R

Computed with RDKit 2025.09.2 from the SMILES returned by PubChem. Audit run 26/09/2026.

Bemis–Murcko scaffold

C1=CCNCC1

Shared with UCD0162. All families

III · Behavior

Behavioral summary

Class, mechanism, and the duration of acute effects — each quoted from the record or trial that publishes it. Duration of effects and plasma half-life are shown separately, because they are different quantities and diverge by a factor of three or four.

Classification

Cholinergic Agonists

Duration of acute subjective effects

—

No controlled human trial reporting a duration for this compound is cited here. The archive holds no other record of one either. A duration is not inferred from a chemical relative.

Plasma elimination half-life

How fast the body clears the drug — not how long the effects last. The two diverge sharply: LSD is cleared with a half-life of about 2.6 h while its subjective effects run 8–12 h.

No half-life is published for this compound in the sources this site reads.

Primary pharmacological drivers

ChEMBL holds no curated mechanism-of-action record for this compound. The measured affinities below are the evidence this archive has for what it binds.

IV · Clinical

Clinical description

Where this compound's substance class sits in ICD-11 and DSM-5-TR, and how much of the recorded literature speaks to each domain of a mental status examination.

No diagnostic chapter is shown for this compound. Either PubChem records no MeSH pharmacological class for it, or the class it records is not one of the substance classes ICD-11 gives a chapter to. Inferring a chapter from the compound’s name or its binding profile would be a diagnosis this archive is in no position to make.

How much has been written about each domain

The clinical domains, and how many of the records this archive holds for this compound say something under each. What the terms mean, and the word list behind every spoke, are set out in the method.

This measures the literature, not the compound. Each spoke counts how many of the 1 records this archive holds for this compound say something under that domain — 1 at the widest ring. A long spoke means the subject has been written about, not that the effect is strong, and a spoke at the center means nothing here discusses it rather than that nothing happens. The terms behind each domain are listed in the method.

Cognition 1: matched on “concentrat” · in Toxicology: Toxin and Toxin Target Database (T3DB)

VI · Profile

Affinity rosette

The strongest measurement at each of 3 molecular targets. Cell-line and whole-organism screens are excluded here — they carry no affinity — and appear in the table below.

Fig. Radius is pX = −log₁₀(value in M), that is 9 − log₁₀(value in nM), computed from the normalized measurement. Hatched wedges are equilibrium binding constants (K_i, K_d); dashed outlines are functional readouts (IC₅₀, EC₅₀, AC₅₀, potency), which answer a different question and are not pooled with them. Rings mark whole pX units from 5 to 10, labeled every second ring in the gutter at the top. Where a target carries several measurements, the strongest is drawn.

VII · Toxicology

Toxicological profile

What has been measured, and what has been published — kept apart, and neither scored. There is no risk rating on this page; the archive once carried one, identical for every compound, produced by a stub.

Measured in this archive

Assays that bear on toxicity, drawn from the same ChEMBL records as everything else on this page. They are measurements of what a compound binds or does to cells — not verdicts about what it does to a person.

No hERG, cytochrome, cytotoxicity or transport measurement exists for Arecoline in this archive.

As published

Quoted verbatim from the database named after each passage, never summarized — a summary of a toxicology statement is a new claim.

Toxicity Summary

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 c…
Toxin and Toxin Target Database (T3DB)

Published passages via PubChem toxicology sections, aggregating Hazardous Substances Data Bank (HSDB), RTECS, LiverTox. No figure on this page is scored, ranked or combined into a risk level.

VIII · Evidence

Every measurement

One row per published value. The identifier in the last column resolves to the ChEMBL assay record it was read from.

Equilibrium binding constants 27

Ki and Kd — a concentration at equilibrium. Directly comparable across rows at the same target.

Target	Class	Type	Value (nM)	pX	Organism	Assay
M2	Unclassified	Ki	2.40	8.62	HUMAN	PMID 12747793
M1	Unclassified	Ki	4.10	8.39	HUMAN	PMID 1704434
Muscarinic acetylcholine receptor	Cholinergic receptors	Ki	5.30	8.28	Rattus norvegicus	CHEMBL747587
Unchecked	Unclassified	Ki	7.40	8.13	— organism not recorded	CHEMBL747590
M1	Unclassified	Ki	29.00	7.54	HUMAN	PMID 12747793
Muscarinic acetylcholine receptor	Cholinergic receptors	Ki	31.00	7.51	Rattus norvegicus	CHEMBL741873
M2	Unclassified	Ki	40.00	7.40	Rattus norvegicus	CHEMBL745149
M3	Unclassified	Ki	43.00	7.37	HUMAN	PMID 12747793
M5	Unclassified	Ki	56.00	7.25	HUMAN	PMID 12747793
M4	Unclassified	Ki	60.00	7.22	HUMAN	PMID 12747793
Neuronal acetylcholine receptor	Cholinergic receptors	Ki	224	6.65	Rattus norvegicus	CHEMBL748021
Neuronal acetylcholine receptor; alpha4/beta2	Cholinergic receptors	Ki	270	6.57	Rattus norvegicus	CHEMBL756005
Neuronal acetylcholine receptor; alpha4/beta2	Cholinergic receptors	Ki	270	6.57	Rattus norvegicus	CHEMBL756007
Muscarinic acetylcholine receptor	Cholinergic receptors	Ki	1,900	5.72	Rattus norvegicus	CHEMBL747588
M2	Unclassified	Ki	2,400	5.62	Homo sapiens	CHEMBL748894
M4	Unclassified	Ki	2,400	5.62	Rattus norvegicus	CHEMBL745526
M2	Unclassified	Ki	5,270	5.28	RAT	PMID 1310135
M3	Unclassified	Ki	5,700	5.24	Rattus norvegicus	CHEMBL742778
M1	Unclassified	Ki	5,950	5.23	RAT	PMID 1310135
Muscarinic acetylcholine receptor	Cholinergic receptors	Ki	7,120	5.15	Rattus norvegicus	CHEMBL747589
M1	Unclassified	Ki	29,000	4.54	Homo sapiens	CHEMBL744768
M3	Unclassified	Ki	43,000	4.37	Homo sapiens	CHEMBL747819
M5	Unclassified	Ki	56,000	4.25	Homo sapiens	CHEMBL747159
M4	Unclassified	Ki	60,000	4.22	Homo sapiens	CHEMBL749861
M1	Unclassified	Ki	86,000	4.07	Rattus norvegicus	CHEMBL1054450
M1	Unclassified	Ki	86,000	4.07	Rattus norvegicus	CHEMBL969250
M1	Unclassified	Ki	88,000	4.06	Rattus norvegicus	CHEMBL1111846

Show all 27 rowsShow first 20

Functional readouts 30

IC₅₀, EC₅₀, AC₅₀ and potency. Assay-dependent, and not interchangeable with a binding constant.

Target	Class	Type	Value (nM)	pX	Organism	Assay
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	1.90	8.72	Rattus norvegicus	CHEMBL747406
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	16.00	7.80	Rattus norvegicus	CHEMBL873442
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	20.00	7.70	Rattus norvegicus	CHEMBL747405
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	24.00	7.62	Rattus norvegicus	CHEMBL845360
M2	Unclassified	EC50	25.00	7.60	Homo sapiens	CHEMBL744783
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	62.70	7.20	Rattus norvegicus	CHEMBL752314
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	77.00	7.11	Rattus norvegicus	CHEMBL747450
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	115	6.94	Rattus norvegicus	CHEMBL747408
M4	Unclassified	EC50	130	6.89	Homo sapiens	CHEMBL749231
M3	Unclassified	EC50	340	6.47	Homo sapiens	CHEMBL746366
M2	Unclassified	IC50	590	6.23	Rattus norvegicus	CHEMBL745720
M5	Unclassified	EC50	600	6.22	Homo sapiens	CHEMBL747137
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	1,000	6.00	Rattus norvegicus	CHEMBL748850
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	1,000	6.00	Rattus norvegicus	CHEMBL714426
Unchecked	Unclassified	IC50	1,000	6.00	— organism not recorded	CHEMBL744383
M1	Unclassified	IC50	1,100	5.96	Rattus norvegicus	CHEMBL752317
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	1,700	5.77	Rattus norvegicus	CHEMBL744134
M1	Unclassified	IC50	1,738	5.76	Rattus norvegicus	CHEMBL857187
M1	Unclassified	IC50	1,740	5.76	Rattus norvegicus	CHEMBL752316
M2	Unclassified	IC50	1,800	5.74	Homo sapiens	CHEMBL748246
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	2,100	5.68	Rattus norvegicus	CHEMBL744132
M1	Unclassified	EC50	3,200	5.49	Homo sapiens	CHEMBL744231
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	5,600	5.25	Rattus norvegicus	CHEMBL747407
M2	Unclassified	IC50	11,000	4.96	Rattus norvegicus	CHEMBL744024
M3	Unclassified	IC50	11,000	4.96	Homo sapiens	CHEMBL746514
M1	Unclassified	IC50	11,920	4.92	Rattus norvegicus	CHEMBL748851
M4	Unclassified	IC50	13,500	4.87	Homo sapiens	CHEMBL749238
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	25,400	4.60	Rattus norvegicus	CHEMBL747409
Muscarinic acetylcholine receptor	Cholinergic receptors	IC50	28,000	4.55	Rattus norvegicus	CHEMBL744133
M1	Unclassified	IC50	65,000	4.19	Homo sapiens	CHEMBL744321

Show all 30 rowsShow first 20

P: PubChem
C: ChEMBL
R: Computed here with RDKit
D: Derived here from the stored measurement

IX · Trials

Registered clinical trials

Studies filed with ClinicalTrials.gov that name this compound as an intervention. A registered trial is a protocol, not a result — status and enrollment are printed beside every row, and withdrawn studies are counted rather than hidden.

— No registered study names Arecoline as an intervention. That is an absence of registered research, not evidence about the compound. Most of this archive has never been the subject of a registered trial.

Records from ClinicalTrials.gov (U.S. National Library of Medicine, NIH), API v2. A study is listed against a compound only when a verified name for that compound appears as a whole word in one of the study's own intervention names. A short code must appear as written, and a name the registry uses for something else (Aleph, a vaccine maker) is not matched. Title matches are not accepted. The matched name and the intervention text it matched are shown with every row.

Searched as Arecoline · Arecholine · Methylarecaiden. Run this search at the registry.

A registered trial is a protocol somebody filed with the registry. It is not a result, and nothing on this plate says whether Arecoline worked.

X · Legal

Controlled-substance status

United States federal scheduling, read from the DEA records this archive holds. Not legal advice, and an absent record is not a finding that a compound is uncontrolled.

No DEA record heldNot the same as unscheduled — see below.

An absent DEA record is not a finding that Arecoline is legal. It means this archive holds no DEA passage for it. The Controlled Substances Analogue Enforcement Act reaches substances that appear on no schedule by name, and many compounds here are ring-substituted analogues of scheduled drugs. Nothing on this plate should be read as saying a compound may lawfully be made, held or supplied.

United States federal status only. State law differs, and so does the law of every other country — none of it is represented here. Scheduling changes, and this reflects the DEA records held by PubChem descriptive sections when the monograph was last harvested, not necessarily today. This is a record of what a database publishes, not legal advice.

XI · Literature

Sources behind this dossier

The papers this compound's values were read from, ranked by what each contributed. Not a review of the field.

Every paper below is one some value on this page came from — a binding constant, a passage of pharmacology or toxicology, or a measured duration. Each entry says what this archive took from it. Nothing else is claimed about any of them: the title is the study’s own account of itself, and a summary written here would be an assertion with no source behind it.

01
C(8) substituted 1-azabicyclo[3.3.1]non-3-enes and C(8) substituted 1-azabicyclo[3.3.1]nonan-4-ones: novel muscarinic receptor antagonists
Kim MG, Bodor ET, Wang C et al. · Journal of medicinal chemistry 2003
- · 5 measurements at 5 targets (Ki), strongest M2 at 8.62 pX
PMID 12747793
02
Pharmacological characterization of a novel muscarinic partial agonist, YM796, in transfected cells expressing the m1 or m2 muscarinic receptor gene
Wei HB, Roeske WR, Lai J et al. · Life sciences 1992
- · 2 measurements at 2 targets (Ki), strongest M2 at 5.28 pX
PMID 1310135
03
Pharmacologic comparison of selected agonists for the M1 muscarinic receptor in transfected murine fibroblast cells (B82)
Mei L, Lai J, Yamamura HI et al. · The Journal of pharmacology and experimental therapeutics 1991
- · 1 measurement at 1 target (Ki), strongest M1 at 8.39 pX
PMID 1704434