Arecoline is a cholinergic agent,

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

, and

naturally occurring A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

found in areca (betel) nuts of the areca palm (''Areca catechu'') found in

South South is one of the cardinal directions or compass points. The direction is the opposite of north and is perpendicular to both west and east. Etymology The word ''south'' comes from Old English ''sūþ'', from earlier Proto-Germanic ''*sunþa ...

and

Southeast Asia Southeast Asia is the geographical United Nations geoscheme for Asia#South-eastern Asia, southeastern region of Asia, consisting of the regions that are situated south of China, east of the Indian subcontinent, and northwest of the Mainland Au ...

. Its effects, depending on the dose, include

stimulation Stimulation is the encouragement of development or the cause of activity in general. For example, "The press provides stimulation of political discourse." An interesting or fun activity can be described as "stimulating", regardless of its physic ...

alertness Alertness is a state of active attention characterized by high sensory awareness. Someone who is alert is vigilant and promptly meets danger or emergency, or is quick to perceive and act. Alertness is a psychological and physiological state. Lac ...

, increased

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

, cognitive enhancement, elation,

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

, pro-sexual effects, relaxation, reduced anxiety, and

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, as well as

addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...

and withdrawal symptoms upon

discontinuation Medication discontinuation is the ceasing of a medication treatment for a patient by either the clinician or the patient themself. When initiated by the clinician, it is known as deprescribing. Medication discontinuation is an important medical ...

. Its effects are described as subtle and it has been likened to a strong cup of

coffee Coffee is a beverage brewed from roasted, ground coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulating effect on humans, primarily due to its caffeine content, but decaffeinated coffee is also commercially a ...

. There are also active constituents of areca nuts, but arecoline is the key active component, with a percentage of ~0.3 to 0.6%. Areca nuts are administered by

chewing Chewing or mastication is the process by which food is crushed and ground by the teeth. It is the first step in the process of digestion, allowing a greater surface area for digestive enzymes to break down the foods. During the mastication proc ...

for 5 to 20minutes without

swallowing Swallowing, also called deglutition or inglutition in scientific and medical contexts, is a physical process of an animal's digestive tract (e.g. that of a human body) that allows for an ingested substance (typically food) to pass from the mou ...

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of arecoline include

hypersalivation Hypersalivation or hypersialosis is the excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva.Medscape > HypersalivationBy Erica Brownfield. P ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

, and

bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

, among others. Other adverse effects can include extrapyramidal syndrome and

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s. Addiction and dependence can occur, with withdrawal symptoms including

mood swing A mood swing is an extreme or sudden change of mood. Such changes can play a positive or a disruptive part in promoting problem solving and in producing flexible forward planning. When mood swings are severe, they may be categorized as part ...

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

irritability Irritability is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimul ...

, and

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

. Rarely,

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

can occur during withdrawal in heavy users. Areca nut use, the primary method of consuming arecoline, is highly associated with oral disease and

oral cancer Oral cancer, also known as oral cavity cancer, tongue cancer or mouth cancer, is a cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless red or white patch, that thickens, gets ulcerated ...

Overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

of arecoline can be treated with antimuscarinic drugs like

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ...

. The drug acts as a non-selective

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

muscarinic A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...

and

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...

s. The major

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of arecoline,

arecaidine Arecaidine is a bio-active alkaloid in areca nuts. It is a competitive GABA reuptake inhibitor. Lime is said to hydrolyse arecoline to arecaidine References

{{GABA metabolism and transport modulators Piperidine alkaloids Beta-Amino acid ...

, is a

GABA reuptake inhibitor A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs). This in turn leads to incr ...

. The subjective effects of arecoline appear to be mediated by muscarinic acetylcholine receptors and not by nicotinic acetylcholine receptors based on

animal studies Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including art history, anthropology ...

. However, its

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

is still yet to be fully understood and other activities have also been described. The stimulant and addictive effects of arecoline are thought to be due to increased

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...

in the

mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The v ...

of the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

. In terms of

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

, arecoline is closely related to

nicotinic acid Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Nicotinic acid is also a prescription medication. Amounts f ...

. The use of arecoline, in the form of areca nuts, dates back several thousand years, including in

Thailand Thailand, officially the Kingdom of Thailand and historically known as Siam (the official name until 1939), is a country in Southeast Asia on the Mainland Southeast Asia, Indochinese Peninsula. With a population of almost 66 million, it spa ...

China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...

, and

Polynesia Polynesia ( , ) is a subregion of Oceania, made up of more than 1,000 islands scattered over the central and southern Pacific Ocean. The indigenous people who inhabit the islands of Polynesia are called Polynesians. They have many things in ...

. Arecoline was first isolated in 1888 and its

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organi ...

was first proposed in 1891, with its

confirmed in 1907. Arecoline, in the form of areca nuts, is used by more than 600million people worldwide (~10–20% of the global population), and is the fourth most commonly used

psychoactive drug A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

in the world after

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

, and

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

. Despite

globalization Globalization is the process of increasing interdependence and integration among the economies, markets, societies, and cultures of different countries worldwide. This is made possible by the reduction of barriers to international trade, th ...

, arecoline is unusual among

recreational drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

s in that its use is still predominantly confined to

Asia Asia ( , ) is the largest continent in the world by both land area and population. It covers an area of more than 44 million square kilometres, about 30% of Earth's total land area and 8% of Earth's total surface area. The continent, which ...

, though its use has been increasing and spreading in part due to the

Internet The Internet (or internet) is the Global network, global system of interconnected computer networks that uses the Internet protocol suite (TCP/IP) to communicate between networks and devices. It is a internetworking, network of networks ...

. Chewing areca nuts is said to be as familiar to various Asian peoples as chewing gum is to Americans. The countries in which areca nut production are highest include

India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...

Myanmar Myanmar, officially the Republic of the Union of Myanmar; and also referred to as Burma (the official English name until 1989), is a country in northwest Southeast Asia. It is the largest country by area in Mainland Southeast Asia and has ...

Malaysia Malaysia is a country in Southeast Asia. Featuring the Tanjung Piai, southernmost point of continental Eurasia, it is a federation, federal constitutional monarchy consisting of States and federal territories of Malaysia, 13 states and thre ...

Indonesia Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania, between the Indian Ocean, Indian and Pacific Ocean, Pacific oceans. Comprising over List of islands of Indonesia, 17,000 islands, including Sumatra, ...

, and

Bangladesh Bangladesh, officially the People's Republic of Bangladesh, is a country in South Asia. It is the List of countries and dependencies by population, eighth-most populous country in the world and among the List of countries and dependencies by ...

. Arecoline and areca nut sale and consumption are not generally controlled throughout the world, with a few exceptions.

Uses

Recreational

In many Asian cultures, the

areca nut The areca nut ( or ) or betel nut () is the fruit of the areca palm (''Areca catechu''). The palm is originally native to the Philippines, but was carried widely through the tropics by the Austronesian migrations and trade since at least 15 ...

is chewed along with betel leaf to obtain a stimulating effect.

Medical

Arecoline has been used medicinally as an

antihelmintic Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them without causing significant damage to the host. They may also ...

(a drug against parasitic worms). It paralyzes tapeworms.

Traditional medicine

Arecoline has been used in

traditional medicine Traditional medicine (also known as indigenous medicine or folk medicine) refers to the knowledge, skills, and practices rooted in the cultural beliefs of various societies, especially Indigenous groups, used for maintaining health and treatin ...

for thousands of years.

Toxicity

The of arecoline is 100 mg/kg, when administered subcutaneously in mice. The minimum lethal dose (MLD) values of arecoline in mice, dogs, and horses is 100 mg/kg, 5 mg/kg and 1.4 mg/kg respectively. It causes oral submucous fibrosis by stimulating collagen, interleukin 6, keratinocyte growth factor-1, IGF-1, cystatin C, tissue inhibitor of matrix metalloproteinases in the mouth. Current science is confident that areca nut chewing is carcinogenic. Research suggests this 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

nitrosamine Nitrosamines (or more formally ''N''-nitrosamines) are organic compounds produced by industrial processes. The chemical structure is , where R is usually an alkyl group. Nitrosamines have a nitroso group () that are "probable human carcinogens", ...

s 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. * ..

The toxicity of arecoline can be partially mitigated by vitamins C and E in mice.

Mechanisms of toxicity

Arecoline is "obviously cytotoxic" to cultures of hepatocytes, bone marrow cells, lymphocytes, neuronal cell, myoblasts and endothelial cells. Arecoline generates excessive

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(ROS) in a number of cell types, including oral epithelial cells and neuronal cells. In adult mice, arecoline is toxic to the testes and liver via ROS generation. Arecoline is also genotoxic, being able to induce DNA damage and mutation in several cell cultures. Mice chronically exposed to arecoline show relaxation of their

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

structure.

Pharmacology

Pharmacodynamics

Arecoline is the primary active ingredient responsible for the central nervous system effects of the areca nut. Arecoline has been compared to

; however, nicotine agonizes

nicotinic acetylcholine receptors Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

, whereas arecoline is primarily a partial agonist of muscarinic acetylcholine receptors, leading to its

parasympathetic The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The autonomic nervous system is responsible for regulat ...

effects. In

frogs A frog is any member of a diverse and largely semiaquatic group of short-bodied, tailless amphibian vertebrates composing the order Anura (coming from the Ancient Greek , literally 'without tail'). Frog species with rough skin texture due to ...

, arecoline also acts as an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.α4 and α6-containing

and as a silent antagonist at α7 nicotinic receptors, which may account for its anti-inflammatory activity. Arecoline also inhibits AMPK through generation of ROS in several types of cells. AN (Areca Nut) is a vasodilator mainly due to the presence of arecoline. It also has anti-thrombosis and anti-atherogenic effects by increasing plasma nitric oxide, eNos, and mRNA expression and decreasing IL-8 along with other downregulations. It increases the level of testosterone by stimulating Leydig's cells as well as levels of FSH and LH. It also activates HPA axis and stimulates CRH release. It prevents the dysfunction of B cells of the pancreas from high fructose intake. Arecoline has the ability to stimulate the digestive system through the activation of

muscarinic receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

s. Areca nut water extract could increase the contractions of gastric smooth muscle and muscle strips of the duodenum, ileum, and colon significantly. This activity could be caused by arecoline.

Pharmacokinetics

Arecoline is metabolized by both kidneys and liver. Currently, 11 metabolites of arecoline are documented among which ''N''-methylnipecotic acid was found to be a major metabolite of both arecoline and

arecaidine Arecaidine is a bio-active alkaloid in areca nuts. It is a competitive GABA reuptake inhibitor. Lime is said to hydrolyse arecoline to arecaidine References

{{GABA metabolism and transport modulators Piperidine alkaloids Beta-Amino acid ...

. Lime, which is traditionally mixed to crushed areca nuts prior to consumption, is said to hydrolyse almost all arecoline to

arecaidine Arecaidine is a bio-active alkaloid in areca nuts. It is a competitive GABA reuptake inhibitor. Lime is said to hydrolyse arecoline to arecaidine References

{{GABA metabolism and transport modulators Piperidine alkaloids Beta-Amino acid ...

, a GABA reuptake inhibitor. Arecaidine is also formed during liver metabolism of arecoline in rats. Arecoline is very efficiently absorbed through oral musoca, with 85% bioavailbility. Maximum plasma concentration is reached within 3 minutes. Orally ingested arecoline is extensively metabolized in rats, with the vast majority of the dose being converted to arecaidine and arecoline ''N''-oxide.

Chemistry

Arecoline is a colorless odorless oily liquid. It 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 organic chemistry, ethers are a class of compounds that contain an ether group, a single oxygen atom bonded to two separate carbon atoms, each part of an organyl group (e.g., alkyl or aryl). They have the general formula , where R and R� ...

in presence of dissolved salts. Being basic, arecoline forms salts with acids. The salts are crystalline, but usually

deliquescent Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption (chemistry), absorption or adsorption from the surrounding Natural environment, environment, which is usually at normal or room temperature. If water mol ...

: the hydrochloride, arecoline•HCl, forms needles, m.p. 158 °C; the hydrobromide, arecoline•HBr, forms slender prisms, mp. 177–179 °C from hot

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...

; the aurichloride, arecoline•HAuCl₄, is an oil, but the platinichloride, arecoline₂•H₂PtCl₆, mp. 176 °C, crystallizes from water in orange-red rhombohedrons. The

methiodide In organic chemistry, a methiodide is a chemical derivative produced by the reaction of a compound with methyl iodide. Methiodides are often formed through the methylation of tertiary amines: : R3N + CH3I → (CH3)R3N+I− Whereas the parent am ...

forms glancing prisms, mp. 173–174 °C.

Synthesis

Although an older method was described in the patent literature, this is less attractive than the modern methods. Arecoline synthesis

Fischer esterification of

(niacin) (1) gives methyl nicotinate (2). Alkylation with

methyl iodide Iodomethane, also called methyl iodide, and commonly abbreviated "MeI", is the chemical compound with the formula CH3I. It is a dense, colorless, volatile liquid. In terms of chemical structure, it is related to methane by replacement of one h ...

then gives 3-methoxycarbonyl-1-methylpyridinium iodide (3). Hydride reduction with an agent such as potassium borohydride thus gives the tetrahydropyridine (4). Salt formation with HBr completes the synthesis (5). Arecoline synthesis2

A double Mannich reaction between methylamine (1), acetaldehyde (2) and formaldehyde (3) in the presence of hydroxylamine hydrochloride is supposed to have delivered 1-methyl-1,2,5,6-tetrahydropyridine-3-carbaldehyde oxime hydrochloride (4) as the product. Dehydration of the aldoxime to the nitrile occurs upon treatment with acetic anhydride giving 3-cyano-1-methyl-1,2,5,6-tetrahydropyridine (5). Functional group interconversion of the nitrile to the methyl carboxylate ester then occurs upon acid-catalyzed treatment in methanol, and then conversion to the HBr salt completes the synthesis.

Chemical precursor

Arecoline is used in the

of a variety of other

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

s, including

paroxetine Paroxetine ( ), sold under the brand name Paxil among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, obsessive-compulsive disorder, o ...

, femoxetine, nocaine, piquindone
PC10058081
( epiboxidine type)
FT-0731096
14724-56-0 piper- brasofensine piper-

Tesofensine Tesofensine (NS2330) is a serotonin-noradrenaline-dopamine reuptake inhibitor, serotonin–noradrenaline–dopamine reuptake inhibitor from the phenyltropane family of drugs, which is being developed for the treatment of obesity. Tesofensine was ...

an
BRN 0023391
02206-67-7

Analogues

Analogues of and related compounds to arecoline include

arecaidine Arecaidine is a bio-active alkaloid in areca nuts. It is a competitive GABA reuptake inhibitor. Lime is said to hydrolyse arecoline to arecaidine References

{{GABA metabolism and transport modulators Piperidine alkaloids Beta-Amino acid ...

, guavacoline, guvacine, nipecotic acid,

muscarine Muscarine, L-(+)-muscarine, or muscarin is a Secondary metabolite, natural product found in certain mushrooms, particularly in ''Inocybe'' and ''Clitocybe'' species, such as the deadly ''Clitocybe dealbata, C. dealbata''. Mushrooms in the g ...

, SKF-89976A, tiagabine, and CI-966. Xanomeline, the anti-schizophrenia component in the approved drug xanomeline/trospium chloride, also has structural similarities to arecoline.

Research

Owing to its

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. Arecoline administered intravenously did indeed show modest verbal and spatial memory improvement in Alzheimer's patients, though due to arecoline's possible carcinogenic properties (see ), it is not the first drug of choice for this degenerative disease. Anecdotal reports indicate that it has a short-lived effect against schizophrenia. Among male schizophrenia patients, higher areca nut consumption is associated with weaker symptoms. It inspired the development of xanomeline. It enhances learning and memory in rodents.

Veterinary use

In 2012, Chinese Ministry of Agriculture listed arecoline hydrobromide as an abolished

veterinary drug An animal drug (also veterinary drug) refers to a drug intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in animals. Regulation United States The U.S. Food and Drug Administration (FDA) has the broad mandat ...

and stopped its production and use.

References

{{Nicotinic acetylcholine receptor modulators Alkaloids Carboxylate esters Euphoriants IARC Group 2B carcinogens M1 receptor agonists M2 receptor agonists M3 receptor agonists M4 receptor agonists M5 receptor agonists Methyl esters Nicotinic agonists Nootropics Plant toxins Stimulants Tetrahydropyridines