A serotonin receptor agonist is an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...

of one or more

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory ne ...

s. They activate serotonin receptors in a manner similar to that of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

(5-hydroxytryptamine; 5-HT), a

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...

and

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...

and the

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, ...

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elect ...

of the serotonin receptors.

Non-selective agonists

Serotonergic psychedelics such as

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...

s (e.g.,

psilocybin Psilocybin ( , ) is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of the genus ''Psilocybe'', such as '' P. azurescens'', '' P. semilanceata'', and '' P.&nbs ...

, psilocin, ,

5-MeO-DMT 5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine) or O-methyl-bufotenin is a psychedelic of the tryptamine class. It is found in a wide variety of plant species, and also is secreted by the glands of at least one toad species, the Colorado R ...

, bufotenin), lysergamides (e.g., , ergine ()),

phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace am ...

s (e.g.,

mescaline Mescaline or mescalin (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, known for its hallucinogenic effects comparable to those of LSD and psilocybin. Biological ...

2C-B 2C-B (4-Bromo-2,5-dimethoxyphenethylamine) is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin in 1974. In Shulgin's book '' PiHKAL'', the dosage range is listed as 12–24 mg. As a recreational drug, 2C-B is so ...

25I-NBOMe 25I-NBOMe (2C-I-NBOMe, Cimbi-5, Smiles and also shortened to "25I") is a synthetic hallucinogen that is used in biochemistry research for mapping the brain's usage of the type 2A serotonin receptor; it is also sometimes used for recreational p ...

), and

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

s (e.g., , ) are non-selective agonists of serotonin receptors. Their

hallucinogen Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorize ...

ic effects are specifically mediated by activation of the 5-HT_2A receptor. Drugs that increase

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

serotonin levels such as serotonin reuptake inhibitors (e.g.,

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive diso ...

venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic ...

), serotonin releasing agents (e.g.,

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome.https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212102s003l ...

, ), and

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, esp ...

s (e.g., phenelzine, moclobemide) are indirect non-selective serotonin receptor agonists. They are used variously as

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

s, antiobsessionals,

appetite suppressant An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" ...

s, and entactogens.

5-HT₁ receptor agonists

5-HT_1A receptor agonists

Azapirone Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). Medical uses Azapirones have shown b ...

s such as buspirone, gepirone, and

tandospirone Tandospirone (brand name Sediel) is an anxiolytic and antidepressant drug used in China and Japan, where it is marketed by Dainippon Sumitomo Pharma. It is a member of the azapirone class of drugs and is closely related to other azapirones li ...

are 5-HT_1A receptor

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

s marketed primarily as

s, but also as

s. The antidepressants

vilazodone Vilazodone, sold under the brand name Viibryd among others, is a medication used to treat major depressive disorder. It is taken Oral administration, by mouth. Common side effects include nausea, diarrhea, and trouble sleeping. Serious side ef ...

and vortioxetine are 5-HT_1A receptor partial agonists.

Flibanserin Flibanserin, sold under the brand name Addyi, is a medication approved for the treatment of pre-menopausal women with hypoactive sexual desire disorder (HSDD). The medication improves sexual desire, increases the number of satisfying sexual even ...

, a drug used for female sexual dysfunction, is a 5-HT_1A receptor partial agonist. Many

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

s, such as aripiprazole, asenapine, clozapine, lurasidone,

quetiapine Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...

, and

ziprasidone Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitati ...

, are 5-HT_1A receptor partial agonists, and this action is thought to contribute to their beneficial effects on negative symptoms in schizophrenia.

5-HT_1B receptor agonists

Triptans such as sumatriptan, rizatriptan, and

naratriptan Naratriptan (trade names include Amerge) is a triptan drug marketed by GlaxoSmithKline and is used for the treatment of migraine headaches. It is a selective 5-HT1 receptor subtype agonist. It was patented in 1987 and approved for medical use ...

are 5-HT_1B receptor agonists that are used to abort

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

and

cluster headache Cluster headache (CH) is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s). There is often accompanying eye watering, nasal congestion, or swelling around the eye on the af ...

attacks. The ergoline antimigraine agent

ergotamine Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural sim ...

also acts on this receptor. Serenics such as batoprazine, eltoprazine, and fluprazine are agonists of the 5-HT_1B receptor and other serotonin receptors, and have been found to produce antiaggressive effects in animals, but have not been marketed. Eltoprazine is under development for the treatment of

aggression Aggression is overt or covert, often harmful, social interaction with the intention of inflicting damage or other harm upon another individual; although it can be channeled into creative and practical outlets for some. It may occur either reacti ...

and for other indications.

5-HT_1D receptor agonists

In addition to being 5-HT_1B agonists, triptans (i.e. sumatriptan, almotriptan, zolmitriptan, naratriptan, eletriptan, frovatriptan and rizatriptan) are also agonists at the 5-HT_1D receptor, which contributes to their antimigraine effect caused by vasoconstriction of blood vessels in the brain. The same is true for ergotamine.

5-HT_1E receptor agonists

The triptan

eletriptan Eletriptan, sold under the brand name Relpax and used in the form of eletriptan hydrobromide, is a second generation triptan medication intended for treatment of migraine headaches. It is used as an abortive medication, blocking a migraine att ...

is an agonist of the 5-HT_1E receptor.

BRL-54443 BRL-54443 is a drug which acts as a selective agonist for the 5-HT1E and 5-HT1F serotonin receptor Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve ...

is a selective 5-HT_1E and 5-HT_1F receptor agonist which is used in

scientific research The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...

5-HT_1F receptor agonists

Triptans such as eletriptan, naratriptan, and sumatriptan are agonists of the 5-HT_1F receptor.

Lasmiditan Lasmiditan, sold under the brand name Reyvow, is a medication used for the acute (active but short-term) treatment of migraine with or without aura (a sensory phenomenon or visual disturbance) in adults. It is not useful for prevention. It is t ...

is a selective 5-HT_1F agonist that is under development by

Eli Lilly and Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...

for the treatment of migraine.

5-HT₂ receptor agonists

5-HT_2A receptor agonists

Serotonergic psychedelics like psilocybin, LSD, and mescaline act as 5-HT_2A receptor agonists. Their actions at this receptor are thought to be responsible for their

ic effects. Most of these drugs also act as agonists of other serotonin receptors. Not all 5-HT_2A receptor agonists are

psychoactive A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

. The

25-NB The 25-NB (25''x''-NB''x'') series, sometimes alternatively referred to as the NBOMe compounds, is a family of serotonergic psychedelics. They are substituted phenethylamines and were derived from the 2C family. They act as selective agonists o ...

(NBOMe) series is a family of phenethylamine serotonergic psychedelics that, unlike other classes of serotonergic psychedelics, act as highly selective 5-HT_2A receptor agonists. The most well-known member of the 25-NB series is

. (2''S'',6''S'')-DMBMPP is an analogue of the 25-NB compounds and is the most highly selective agonist of the 5-HT_2A receptor that has been identified to date.

O-4310 O-4310 (1-isopropyl-6-fluoro-psilocin) is a tryptamine derivative developed by Organix Inc which acts as a serotonin receptor agonist. It is claimed to have an EC50 of 5nM at 5-HT2A with 89% efficacy vs 5-HT, and 100x selectivity over 5-HT2C, ...

(1-isopropyl-6-fluoropsilocin) is a tryptamine derivative that is a highly selective agonist of the 5-HT_2A receptor. Selective 5-HT_2A receptor agonists like the 25-NB compounds, specifically those which can behave as full agonists at this receptor, can cause

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...

-like

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term compl ...

s such as

hyperthermia Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extrem ...

, hyperpyrexia,

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...

, clonus,

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

s, agitation,

, and

hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...

s which has ended in death on numerous occasions despite these particular drugs only being available to drug users for about 2–3 years, being widely in use mostly in the period from 2010-2012. Bans were put in place around 2012-2013 by countries where they had risen to popularity. They quickly and often accidentally lead to

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.

. In contrast to the aforementioned drugs's potent, selective, and most importantly, full agonism (meaning the drug can fully activate the receptor to 100% of its activation potential, and does so even with minuscule amounts due to high potency, LSD, like the other "safe" psychedelics which are almost impossible to overdose fatally on, is a partial agonist, and this means it has a limit of how much it can activate the receptor, a limit which is basically impossible to exceed even with exponentially larger amounts of the drug. These partial agonists have proven relatively safe after having seen widespread abuse by drug users for many decades. Activation of the 5-HT_2A receptor is also implicated in serotonin syndrome caused by indirect serotonin receptor agonists like serotonin reuptake inhibitors, serotonin releasing agents, and monoamine oxidase inhibitors. Antagonists of the 5-HT_2A receptor like

cyproheptadine Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine, first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties. It was patented in 1959 an ...

and chlorpromazine are able to reverse and mediate recovery from serotonin syndrome.

5-HT_2B receptor agonists

Agonists of the 5-HT_2B receptor are implicated in the development of cardiac fibrosis.Hutcheson, J. D., Setola, V., Roth, B. L., & Merryman, W. D. (2011). Serotonin receptors and heart valve disease—it was meant 2B. Pharmacology & Therapeutics, 132(2), 146-157.

Fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome.https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212102s003l ...

, pergolide, and cabergoline have been withdrawn from some markets for this reason. Many serotonergic psychedelics, such as LSD and psilocin, have been shown to activate this receptor directly. MDMA has been reported to be both a potent direct agonist and have an indirect effect by increasing plasma serotonin levels.Zolkowska, D., Rothman, R. B., & Baumann, M. H. (2006). Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. Journal of Pharmacology and Experimental Therapeutics, 318(2), 604-610.

5-HT_2C receptor agonists

Lorcaserin is an

and

anti-obesity drug Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control weight. These medications alter one of the fundamental processes of the human body, weight regulation, by altering either appetite, or absorp ...

which acts as a selective 5-HT_2C receptor agonist. ''meta''-Chlorophenylpiperazine (mCPP) is a 5-HT_2C-preferring serotonin receptor agonist that induces

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

and depression and can cause

panic attack Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...

s in susceptible individuals.

5-HT₃ receptor agonists

2-Methyl-5-hydroxytryptamine 2-Methyl-5-hydroxytryptamine (2-Methylserotonin, 2-Methyl-5-HT) is a tryptamine derivative closely related to the neurotransmitter serotonin which acts as a moderately selective full agonist at the 5-HT3 receptor. See also * 5-Carboxamidotry ...

(2-methylserotonin) and quipazine are moderately selective agonists of the 5-HT₃ receptor that are used in scientific research. Agonists of this receptor are known to induce

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

, and are not used medically.

5-HT₄ receptor agonists

Cisapride Cisapride is a gastroprokinetic agent, a drug that increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors in ...

and tegaserod are 5-HT₄ receptor partial agonists that were used to treat disorders of gastrointestinal motility.

Prucalopride Prucalopride, brand names Resolor and Motegrity among others, is a drug acting as a selective, high affinity 5-HT4 receptor agonist which targets the impaired motility associated with chronic constipation, thus normalizing bowel movements. Pruca ...

is a highly selective 5-HT₄ receptor agonist that can be used to treat certain disorders of gastrointestinal motility. Other 5-HT₄ receptor agonists have shown potential to be

nootropic Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic dietary supplement, supplements or drugs and other substances that are claimed to improve cognitive function ...

and antidepressant drugs, but have not been marketed for such indications.

5-HT_5A receptor agonists

Valerenic acid, a constituent of

valerian root Valerian (''Valeriana officinalis'', Caprifoliaceae) is a perennial flowering plant native to Europe and Asia. In the summer when the mature plant may have a height of , it bears sweetly scented pink or white flowers that attract many fly specie ...

, has been found to act as a 5-HT_5A receptor agonist, and this action could be involved in the sleep-promoting effects of valerian.

5-HT₆ receptor agonists

No selective agonists of the 5-HT₆ receptor have been approved for medical use. Selective 5-HT₆ receptor agonists like E-6801, E-6837, EMDT, WAY-181,187, and WAY-208,466 show antidepressant,

, antiobsessional, and

effects in animals, but also impair

cognition Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, though ...

and

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remember ...

Non-selective agonists

5-HT₁ receptor agonists

5-HT_1A receptor agonists

5-HT_1B receptor agonists

5-HT_1D receptor agonists

5-HT_1E receptor agonists

5-HT_1F receptor agonists

5-HT₂ receptor agonists

5-HT_2A receptor agonists

5-HT_2B receptor agonists

5-HT_2C receptor agonists

5-HT₃ receptor agonists

5-HT₄ receptor agonists

5-HT_5A receptor agonists

5-HT₆ receptor agonists

5-HT₇ receptor agonists

See also

References

External links

Non-selective agonists

5-HT1 receptor agonists

5-HT1A receptor agonists

5-HT1B receptor agonists

5-HT1D receptor agonists

5-HT1E receptor agonists

5-HT1F receptor agonists

5-HT2 receptor agonists

5-HT2A receptor agonists

5-HT2B receptor agonists

5-HT2C receptor agonists

5-HT3 receptor agonists

5-HT4 receptor agonists

5-HT5A receptor agonists

5-HT6 receptor agonists

5-HT7 receptor agonists

See also

References

External links

5-HT₁ receptor agonists

5-HT_1A receptor agonists

5-HT_1B receptor agonists

5-HT_1D receptor agonists

5-HT_1E receptor agonists

5-HT_1F receptor agonists

5-HT₂ receptor agonists

5-HT_2A receptor agonists

5-HT_2B receptor agonists

5-HT_2C receptor agonists

5-HT₃ receptor agonists

5-HT₄ receptor agonists

5-HT_5A receptor agonists

5-HT₆ receptor agonists

5-HT₇ receptor agonists