The Info List - Histamine

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is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological function in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus.[3][4] Histamine
is involved in the inflammatory response and has a central role as a mediator of itching.[5] As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine
increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues.[6]


1 Properties 2 Synthesis and metabolism 3 Storage and release 4 Mechanism of action 5 Roles in the body

5.1 Vasodilation and a fall in blood pressure 5.2 Effects on nasal mucous membrane 5.3 Sleep-wake regulation 5.4 Gastric acid
Gastric acid
release 5.5 Protective effects 5.6 Erection and sexual function 5.7 Schizophrenia 5.8 Multiple sclerosis

6 Disorders 7 History 8 See also 9 References 10 External links

Properties[edit] Histamine
base, obtained as a mineral oil mull, melts at 83–84 °C.[7] Hydrochloride[8] and phosphorus[9] salts form white hygroscopic crystals and are easily dissolved in water or ethanol, but not in ether. In aqueous solution, histamine exists in two tautomeric forms: Nπ-H-histamine and Nτ-H-histamine. The imidazole ring has two nitrogens. The nitrogen farthest away from the side chain is the 'tele' nitrogen and is denoted by a lowercase tau sign. The nitrogen closest to the side chain is the 'pros' nitrogen and is denoted by the pi sign. The position of the nitrogen with the hydrogen on it determines how the tautomer is named. If the nitrogen with the hydrogen is in the tele position, then histamine is in the tele-tautomer form. The tele-tautomer is preferred in solution.

Tautomers of histamine

has two basic centres, namely the aliphatic amino group and whichever nitrogen atom of the imidazole ring does not already have a proton. Under physiological conditions, the aliphatic amino group (having a pKa around 9.4) will be protonated, whereas the second nitrogen of the imidazole ring (pKa ≈ 5.8) will not be protonated.[10] Thus, histamine is normally protonated to a singly charged cation. Histamine
is a monoamine neurotransmitter. Synthesis and metabolism[edit] Histamine
is derived from the decarboxylation of the amino acid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase. It is a hydrophilic vasoactive amine.

Conversion of histidine to histamine by histidine decarboxylase

Once formed, histamine is either stored or rapidly inactivated by its primary degradative enzymes, histamine-N-methyltransferase or diamine oxidase. In the central nervous system, histamine released into the synapses is primarily broken down by histamine-N-methyltransferase, while in other tissues both enzymes may play a role. Several other enzymes, including MAO-B
and ALDH2, further process the immediate metabolites of histamine for excretion or recycling. Bacteria also are capable of producing histamine using histidine decarboxylase enzymes unrelated to those found in animals. A non-infectious form of foodborne disease, scombroid poisoning, is due to histamine production by bacteria in spoiled food, particularly fish. Fermented foods and beverages naturally contain small quantities of histamine due to a similar conversion performed by fermenting bacteria or yeasts. Sake
contains histamine in the 20–40 mg/L range; wines contain it in the 2–10 mg/L range.[11] Storage and release[edit]

Mast cells.

Most histamine in the body is generated in granules in mast cells and in white blood cells (leukocytes) called basophils. Mast cells
Mast cells
are especially numerous at sites of potential injury — the nose, mouth, and feet, internal body surfaces, and blood vessels. Non-mast cell histamine is found in several tissues, including the brain, where it functions as a neurotransmitter. Another important site of histamine storage and release is the enterochromaffin-like (ECL) cell of the stomach. The most important pathophysiologic mechanism of mast cell and basophil histamine release is immunologic. These cells, if sensitized by IgE antibodies attached to their membranes, degranulate when exposed to the appropriate antigen. Certain amines and alkaloids, including such drugs as morphine, and curare alkaloids, can displace histamine in granules and cause its release. Antibiotics like polymyxin are also found to stimulate histamine release. Histamine
release occurs when allergens bind to mast-cell-bound IgE antibodies. Reduction of IgE overproduction may lower the likelihood of allergens finding sufficient free IgE to trigger a mast-cell-release of histamine. Mechanism of action[edit] In humans, histamine exerts its effects primarily by binding to G protein-coupled histamine receptors, designated H1 through H4.[12] As of 2015, histamine is believed to activate ligand-gated chloride channels in the brain and intestinal epithelium.[12][13]

Biological targets of histamine in the human body

G-protein coupled receptor Location Function Sources

H1 receptor

CNS: Expressed on the dendrites of the output neurons of the histaminergic tuberomammillary nucleus, which projects to the dorsal raphe, locus coeruleus, and additional structures. Periphery: Smooth muscle, endothelium, sensory nerves

CNS: Sleep-wake cycle
Sleep-wake cycle
(promotes wakefulness), body temperature, nociception, endocrine homeostasis, regulates appetite, involved in cognition Periphery: Causes bronchoconstriction, bronchial smooth muscle contraction, vasodilation, promotes hypernociception (visceral hypersensitivity), involved in itch perception and urticaria.


H2 receptor

CNS: Dorsal striatum
Dorsal striatum
(caudate nucleus and putamen), cerebral cortex (external layers), hippocampal formation, dentate nucleus of the cerebellum Periphery: Located on parietal cells, vascular smooth muscle cells, neutrophils, mast cells, as well as on cells in the heart and uterus

CNS: Not established (note: most known H2 receptor ligands are unable to cross the blood–brain barrier in sufficient concentrations to allow for neuropsychological and behavioral testing) Periphery: Primarily involved in vasodilation and stimulation of gastric acid secretion. Modulates gastrointestinal function.


H3 receptor Located in the central nervous system and to a lesser extent peripheral nervous system tissue Autoreceptor
and heteroreceptor functions: decreased neurotransmitter release of histamine, acetylcholine, norepinephrine, serotonin Modulates nociception, gastric acid secretion, and food intake. [12]

H4 receptor Located primarily on basophils and in the bone marrow. It is also expressed in the thymus, small intestine, spleen, and colon. Plays a role in mast cell chemotaxis, itch perception, cytokine production and secretion, and visceral hypersensitivity. Other functions (inflammation, allergy, cognition, etc.) have not been fully characterized. [12]

Ligand-gated ion channel Location Function Sources

Histamine-gated chloride channel Putatively: CNS (hypothalamus, thalamus) and intestinal epithelium Brain: Produces fast inhibitory postsynaptic potentials Intestinal epithelium: chloride secretion (associated with secretory diarrhea) [12][13]

Roles in the body[edit] Although histamine is small compared to other biological molecules (containing only 17 atoms), it plays an important role in the body. It is known to be involved in 23 different physiological functions. Histamine
is known to be involved in many physiological functions because of its chemical properties that allow it to be versatile in binding. It is Coulombic (able to carry a charge), conformational, and flexible. This allows it to interact and bind more easily.[16] Vasodilation and a fall in blood pressure[edit] When injected intravenously, histamine causes most blood vessels to dilate, and hence causes a fall in the blood pressure.[17] This is a key mechanism in anaphylaxis, and is thought to be caused when histamine releases nitric oxide, endothelium-derived hyperpolarizing factors and other compounds from the endothelial cells. Effects on nasal mucous membrane [edit] Increased vascular permeability causes fluid to escape from capillaries into the tissues, which leads to the classic symptoms of an allergic reaction: a runny nose and watery eyes. Allergens can bind to IgE-loaded mast cells in the nasal cavity's mucous membranes. This can lead to three clinical responses:[18]

sneezing due to histamine-associated sensory neural stimulation hyper-secretion from glandular tissue nasal congestion due to vascular engorgement associated with vasodilation and increased capillary permeability

Sleep-wake regulation[edit] Histamine
is released as a neurotransmitter. The cell bodies of histamine neurons are found in the posterior hypothalamus, in the tuberomammillary nuclei. From here, these neurons project throughout the brain, including to the cortex, through the medial forebrain bundle. Histamine
neurons increase wakefulness and prevent sleep.[19] Classically, antihistamines (H1 histamine receptor antagonists) which cross the blood-brain barrier produce drowsiness. Newer antihistamines are designed to not cross into the brain and thus are less likely to cause sedation, although individual reactions, concomitant medications and dosage may increase the sedative effect. Similar to the effect of older antihistamines, destruction of histamine releasing neurons, or inhibition of histamine synthesis leads to an inability to maintain vigilance. Finally, H3 receptor antagonists increase wakefulness. Histaminergic neurons have a wakefulness-related firing pattern. They fire rapidly during waking, fire more slowly during periods of relaxation/tiredness and completely stop firing during REM and NREM (non-REM) sleep. Gastric acid
Gastric acid
release[edit] Enterochromaffin-like cells, located within the gastric glands of the stomach, release histamine that stimulates nearby parietal cells by binding to the apical H2 receptor. Stimulation of the parietal cell induces the uptake of carbon dioxide and water from the blood, which is then converted to carbonic acid by the enzyme carbonic anhydrase. Inside the cytoplasm of the parietal cell, the carbonic acid readily dissociates into hydrogen and bicarbonate ions. The bicarbonate ions diffuse back through the basilar membrane and into the bloodstream, while the hydrogen ions are pumped into the lumen of the stomach via a K+/H+ ATPase pump. Histamine
release is halted when the pH of the stomach starts to decrease. Antagonist molecules, like ranitidine, block the H2 receptor and prevent histamine from binding, causing decreased hydrogen ion secretion. Protective effects[edit] While histamine has stimulatory effects upon neurons, it also has suppressive ones that protect against the susceptibility to convulsion, drug sensitization, denervation supersensitivity, ischemic lesions and stress.[20] It has also been suggested that histamine controls the mechanisms by which memories and learning are forgotten.[21] Erection and sexual function[edit] Libido loss and erectile failure can occur during treatment with histamine H2 receptor antagonists such as cimetidine, ranitidine, and risperidone.[22] The injection of histamine into the corpus cavernosum in men with psychogenic impotence produces full or partial erections in 74% of them.[23] It has been suggested that H2 antagonists may cause sexual difficulties by reducing the uptake[clarification needed] of testosterone.[22] Schizophrenia[edit] Metabolites of histamine are increased in the cerebrospinal fluid of people with schizophrenia, while the efficiency of H1 receptor binding sites is decreased. Many atypical antipsychotic medications have the effect of increasing histamine production, because histamine levels seem to be imbalanced in people with that disorder.[24] Multiple sclerosis[edit] Histamine
therapy for treatment of multiple sclerosis is currently being studied. The different H receptors have been known to have different effects on the treatment of this disease. The H1 and H4 receptors, in one study, have been shown to be counterproductive in the treatment of MS. The H1 and H4 receptors are thought to increase permeability in the blood-brain barrier, thus increasing infiltration of unwanted cells in the central nervous system. This can cause inflammation, and MS symptom worsening. The H2 and H3 receptors are thought to be helpful when treating MS patients. Histamine
has been shown to help with T-cell differentiation. This is important because in MS, the body's immune system attacks its own myelin sheaths on nerve cells (which causes loss of signaling function and eventual nerve degeneration). By helping T cells to differentiate, the T cells will be less likely to attack the body's own cells, and instead attack invaders.[25] Disorders[edit] As an integral part of the immune system, histamine may be involved in immune system disorders[26] and allergies. Mastocytosis
is a rare disease in which there is a proliferation of mast cells that produce excess histamine.[27] History[edit] The properties of histamine, then called β-iminazolylethylamine, were first described in 1910 by the British scientists Henry H. Dale and P.P. Laidlaw.[28] By 1913 the name histamine was in use, using combining forms of histo- + amine, yielding "tissue amine". "H substance" or "substance H" are occasionally used in medical literature for histamine or a hypothetical histamine-like diffusible substance released in allergic reactions of skin and in the responses of tissue to inflammation.[citation needed] See also[edit]

Anaphylaxis Diamine oxidase Hay fever (allergic rhinitis) Histamine
intolerance Histamine receptor antagonist Red wine headache Scombroid food poisoning


^ a b Histamine
Material Safety Data Sheet (Technical report). sciencelab.com. 2013-05-21.  ^ a b Vuckovic, Dajana; Pawliszyn, Janusz (15 March 2011). "Systematic Evaluation of Solid-Phase Microextraction Coatings for Untargeted Metabolomic Profiling of Biological Fluids by Liquid Chromatography−Mass Spectrometry". Analytical Chemistry. Supporting Information. 83 (6): 1944–1954. doi:10.1021/ac102614v. PMID 21332182.  ^ Marieb, E. (2001). Human anatomy & physiology. San Francisco: Benjamin Cummings. p. 414. ISBN 0-8053-4989-8.  ^ Nieto-Alamilla, G; Márquez-Gómez, R; García-Gálvez, AM; Morales-Figueroa, GE; Arias-Montaño, JA (November 2016). "The Histamine
H3 Receptor: Structure, Pharmacology, and Function". Molecular Pharmacology. 90 (5): 649–673. doi:10.1124/mol.116.104752. PMID 27563055.  ^ Andersen HH, Elberling J, Arendt-Nielsen L (2015). "Human surrogate models of histaminergic and non-histaminergic itch". Acta Dermato-Venereologica. 95: 771–7. doi:10.2340/00015555-2146. PMID 26015312.  ^ Di Giuseppe, M.; et al. (2003). Nelson Biology 12. Toronto: Thomson Canada. p. 473. ISBN 0-17-625987-2.  ^ "Histamine". webbook.nist.gov.  ^ " Histamine dihydrochloride
Histamine dihydrochloride
H7250". Sigma-Aldrich.  ^ http://lib.njutcm.edu.cn/yaodian/ep/EP501E/16_monographs/17_monographs_d-k/histamine_phosphate/0144e.pdf ^ Paiva, T. B.; Tominaga, M.; Paiva, A. C. M. (1970). "Ionization of histamine, N-acetylhistamine, and their iodinated derivatives". Journal of Medicinal Chemistry. 13 (4): 689–692. doi:10.1021/jm00298a025. PMID 5452432.  ^ http://astrobiology.berkeley.edu/PDFs_articles/WineAnalysisAnalChem.pdf ^ a b c d e f g Panula P, Chazot PL, Cowart M, et al. (2015). "International Union of Basic and Clinical Pharmacology. XCVIII. Histamine
Receptors". Pharmacol. Rev. 67 (3): 601–55. doi:10.1124/pr.114.010249. PMC 4485016 . PMID 26084539.  ^ a b c d Wouters MM, Vicario M, Santos J (2015). "The role of mast cells in functional GI disorders". Gut. 65: 155–168. doi:10.1136/gutjnl-2015-309151. PMID 26194403.  ^ Blandina, Patrizio; Munari, Leonardo; Provensi, Gustavo; Passani, Maria B. (2012). " Histamine
neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations?". Frontiers in Systems Neuroscience. 6. doi:10.3389/fnsys.2012.00033.  ^ Maguire JJ, Davenport AP (29 November 2016). "H2 receptor". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 March 2017.  ^ Noszal, B.; Kraszni, M.; Racz, A. (2004). "Histamine: fundamentals of biological chemistry". In Falus, A.; Grosman, N.; Darvas, Z. Histamine: Biology and Medical Aspects. Budapest: SpringMed. pp. 15–28. ISBN 380557715X.  ^ Dale, HH; Laidlaw, PP (31 December 1910). "The physiological action of beta-iminazolylethylamine". The Journal of Physiology. 41 (5): 318–44. doi:10.1113/jphysiol.1910.sp001406. PMC 1512903 . PMID 16993030.  ^ Monroe EW, Daly AF, Shalhoub RF (February 1997). "Appraisal of the validity of histamine-induced wheal andï flare to predict the clinical efficacy of antihistamines". J. Allergy Clin. Immunol. 99 (2): S798–806. doi:10.1016/s0091-6749(97)70128-3. PMID 9042073.  ^ Brown, RE; Stevens, DR; Haas, HL (2001). "The Physiology of Brain Histamine". Progress in Neurobiology. 63 (6): 637–672. doi:10.1016/s0301-0082(00)00039-3. PMID 11164999.  ^ Yanai, K; Tashiro, M (2007). "The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies". Pharmacology & Therapeutics. 113 (1): 1–15. doi:10.1016/j.pharmthera.2006.06.008. PMID 16890992.  ^ Alvarez, EO (2009). "The role of histamine on cognition". Behavioural Brain
Research. 199 (2): 183–9. doi:10.1016/j.bbr.2008.12.010. PMID 19126417.  ^ a b White, JM; Rumbold, GR (1988). "Behavioural effects of histamine and its antagonists: a review". Psychopharmacology. 95 (1): 1–14. doi:10.1007/bf00212757. PMID 3133686.  ^ Cará, AM; Lopes-Martins, RA; Antunes, E; Nahoum, CR; De Nucci, G (1995). "The role of histamine in human penile erection". British Journal of Urology. 75 (2): 220–4. doi:10.1111/j.1464-410X.1995.tb07315.x. PMID 7850330.  ^ Ito, C (2004). "The role of the central histaminergic system on schizophrenia". Drug News & Perspectives. 17 (6): 383–7. doi:10.1358/dnp.2004.17.6.829029. PMID 15334189. Many atypical antipsychotics also increased histamine turnovers.  ^ Jadidi-Niaragh F, Mirshafiey A (September 2010). " Histamine
and histamine receptors in pathogenesis and treatment of multiple sclerosis". Neuropharmacology. 59 (3): 180–9. doi:10.1016/j.neuropharm.2010.05.005. PMID 20493888.  ^ E. Zampeli; E. Tiligada. "The role of histamine H4 receptor in immune and inflammatory disorders". Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 157: 24–33. doi:10.1111/j.1476-5381.2009.00151.x. PMC 2697784 . PMID 19309354.  ^ Valent P, Horny HP, Escribano L, et al. (July 2001). "Diagnostic criteria and classification of mastocytosis: a consensus proposal". Leuk. Res. 25 (7): 603–25. doi:10.1016/S0145-2126(01)00038-8. PMID 11377686.  ^ Dale HH, Laidlaw PP (December 1910). "The physiological action of β-iminazolylethylamine" (PDF). J. Physiol. 41 (5): 318–44. doi:10.1113/jphysiol.1910.sp001406. PMC 1512903 . PMID 16993030. 

External links[edit]

MS Spectrum DrugBank EXPT01785

bound to proteins in the PDB

v t e

Histamine receptor modulators


Agonists: 2-Pyridylethylamine Betahistine Histamine HTMT L-Histidine UR-AK49

Antagonists: First-generation: 4-Methyldiphenhydramine Alimemazine Antazoline Azatadine Bamipine Benzatropine
(benztropine) Bepotastine Bromazine Brompheniramine Buclizine Captodiame Carbinoxamine Chlorcyclizine Chloropyramine Chlorothen Chlorphenamine Chlorphenoxamine Cinnarizine Clemastine Clobenzepam Clocinizine Cloperastine Cyclizine Cyproheptadine Dacemazine Decloxizine Deptropine Dexbrompheniramine Dexchlorpheniramine Dimenhydrinate Dimetindene Diphenhydramine Diphenylpyraline Doxylamine Embramine Etodroxizine Etybenzatropine
(ethylbenztropine) Etymemazine Fenethazine Flunarizine Histapyrrodine Homochlorcyclizine Hydroxyethylpromethazine Hydroxyzine Isopromethazine Isothipendyl Meclozine Medrylamine Mepyramine
(pyrilamine) Mequitazine Methafurylene Methapyrilene Methdilazine Moxastine Orphenadrine Oxatomide Oxomemazine Perlapine Phenindamine Pheniramine Phenyltoloxamine Pimethixene Piperoxan Pipoxizine Promethazine Propiomazine Pyrrobutamine Talastine Thenalidine Thenyldiamine Thiazinamium Thonzylamine Tolpropamine Tripelennamine Triprolidine

Second/third-generation: Acrivastine Alinastine Astemizole Azelastine Bamirastine Barmastine Bepiastine Bepotastine Bilastine Cabastinen Carebastine Cetirizine Clemastine Clemizole Clobenztropine Desloratadine Dorastine Ebastine Efletirizine Emedastine Epinastine Fexofenadine Flezelastine Ketotifen Latrepirdine Levocabastine Levocetirizine Linetastine Loratadine Mapinastine Mebhydrolin Mizolastine Moxastine Noberastine Octastine Olopatadine Perastine Pibaxizine Piclopastine Quifenadine
(phencarol) Rocastine Rupatadine Setastine Sequifenadine (bicarphen) Talastine Temelastine Terfenadine Vapitadine Zepastine

Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, RP-5063, ziprasidone, zotepine) Phenylpiperazine
antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione) Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline) Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine) Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene)

Unknown/unsorted: Azanator Belarizine Elbanizine Flotrenizine Napactadine Tagorizine Trelnarizine Trenizine


Agonists: Amthamine Betazole Dimaprit Histamine HTMT Impromidine L-Histidine UR-AK49

Antagonists: Bisfentidine Burimamide Cimetidine Dalcotidine Donetidine Ebrotidine Etintidine Famotidine Isolamtidine Lafutidine Lamtidine Lavoltidine
(loxtidine) Lupitidine Metiamide Mifentidine Niperotidine Nizatidine Osutidine Oxmetidine Pibutidine Quisultazine (quisultidine) Ramixotidine Ranitidine Roxatidine Sufotidine Tiotidine Tuvatidine Venritidine Xaltidine Zolantidine


Agonists: α-Methylhistamine Cipralisant Histamine Imetit Immepip Immethridine L-Histidine Methimepip Proxyfan

Antagonists: A-349,821 A-423,579 ABT-239 ABT-652 AZD5213 Bavisant Betahistine Burimamide Ciproxifan Clobenpropit Conessine Enerisant GSK-189,254 Impentamine Iodophenpropit Irdabisant JNJ-5207852 MK-0249 NNC 38-1049 PF-03654746 Pitolisant SCH-79687 Thioperamide VUF-5681


Agonists: 4-Methylhistamine α-Methylhistamine Histamine L-Histidine OUP-16 VUF-8430

Antagonists: JNJ-7777120 Mianserin Seliforant Thioperamide Toreforant VUF-6002

See also: Receptor/signaling modulators • Monoamine metabolism modulators • Monoamine reuptake inhibitors

v t e


Amino acid-derived

Major excitatory/inhibitory systems: Glutamate system: Agmatine Aspartic acid
Aspartic acid
(aspartate) Cycloserine Glutamic acid
Glutamic acid
(glutamate) Glutathione Glycine GSNO GSSG Kynurenic acid NAA NAAG Proline Serine; GABA system: GABA GABOB GHB; Glycine
system: α-Alanine β-Alanine Glycine Hypotaurine Proline Sarcosine Serine Taurine; GHB system: GHB T-HCA (GHC)

Biogenic amines: Monoamines: 6-OHM Dopamine Epinephrine
(adrenaline) NAS (normelatonin) Norepinephrine
(noradrenaline) Serotonin
(5-HT); Trace amines: 3-Iodothyronamine N-Methylphenethylamine N-Methyltryptamine m-Octopamine p-Octopamine Phenylethanolamine Phenethylamine Synephrine Tryptamine m-Tyramine p-Tyramine; Others: Histamine

Neuropeptides: See here instead.


Endocannabinoids: 2-AG 2-AGE (noladin ether) 2-ALPI 2-OG AA-5-HT Anandamide
(AEA) DEA LPI NADA NAGly OEA Oleamide PEA RVD-Hpα SEA Virodhamine

Neurosteroids: See here instead.


Nucleosides: Adenosine
system: Adenosine ADP AMP ATP


Cholinergic system: Acetylcholine


Gasotransmitters: Carbon monoxide
Carbon monoxide
(CO) Hydrogen
sulfide (H2S) Nitric oxide
Nitric oxide
(NO); Candidates: Acetaldehyde Ammonia
(NH3) Carbonyl sulfide
Carbonyl sulfide
(COS) Nitrous oxide
Nitrous oxide
(N2O) Sulfur dioxide
Sulfur dioxide

v t e

Human trace amine-associated receptor ligands




Classical monoamine neurotransmitters

Dopamine Histamine Norepinephrine Serotonin

Trace amines

3-Iodothyronamine 3-Methoxytyramine N-Methylphenethylamine N-Methyltyramine m-Octopamine p-Octopamine Phenethylamine Phenylethanolamine Synephrine Tryptamine m-Tyramine p-Tyramine


Amphetamine DOB DOET 4-Hydroxyamphetamine Isoprenaline MDA (tenamfetamine) MDMA
(midomafetamine) 2-Methylphenethylamine 3-Methylphenethylamine 4-Methylphenethylamine β-Methylphenethylamine Methamphetamine 3-MMA Norfenfluramine Phentermine o-PIT Propylhexedrine RO5166017 N,N-Dimethylphenethylamine

Neutral antagonists


Inverse agonists




3-Iodothyronamine Phenethylamine Tyramine

Neutral antagonists




Dimethylethylamine Trimethylamine

Neutral antagonists


Inverse agonists‡


† References for all endogenous human TAAR1
ligands are provided at List of trace amines

‡ References for synthetic TAAR1
agonists can be found at TAAR1
or in the associated compound articles. For TAAR2
and TAAR5
agonists and inverse agonists, see TAAR for references.

See also: Receptor/signaling modulators

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