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The thyroid gland makes and releases two hormones: triiodothyronine (T3)[o-(4-Hydroxy-3,5-iodophenyl)3,5-diiodophenyl tyrosine]and thyroxine (T4)[o-(4-Hydroxy-3,5-diiodophenyl)3,5diiodophenyl tyrosine]. They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine (see molecular model). A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3.[1] In humans, the ratio of T4 to T3 released into the blood is sometimes claimed to be quite high, but thyroid removal patient data suggests it to vary between 4:1 to 2:1, the average being 100:36 (roughly 2.8:1). T4 is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5'-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). All three isoforms of the deiodinases are selenium-containing enzymes, thus dietary selenium is essential for T3 production. Edward Calvin Kendall was responsible for the isolation of thyroxine in 1915.[2]

Contents

1 Function 2 Medical use

2.1 Formulations

3 Production

3.1 Central 3.2 Peripheral 3.3 Initiation of production in fetuses 3.4 Effect of iodine deficiency on thyroid hormone synthesis

4 Circulation and transport

4.1 Plasma transport 4.2 Membrane transport 4.3 Intracellular transport

5 Mechanism of action

5.1 Thyroxine, iodine and apoptosis 5.2 Effects of triiodothyronine

6 Measurement 7 Related diseases 8 Anti-thyroid drugs 9 See also 10 References 11 External links

Function[edit]

The thyroid system of the thyroid hormones T3 and T4.[3]

The thyroid hormones act on nearly every cell in the body. They act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neural maturation, and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis. Thyroid
Thyroid
hormone leads to heat generation in humans. However, the thyronamines function via some unknown mechanism to inhibit neuronal activity; this plays an important role in the hibernation cycles of mammals and the moulting behaviour of birds. One effect of administering the thyronamines is a severe drop in body temperature..... Medical use[edit] Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally. Levothyroxine
Levothyroxine
is the pharmaceutical name of the manufactured version of T4, which is metabolised more slowly than T3 and hence usually only needs once-daily administration. Natural desiccated thyroid hormones are derived from pig thyroid glands, and are a "natural" hypothyroid treatment containing 20% T3 and traces of T2, T1and calcitonin. Also available are synthetic combinations of T3/T4 in different ratios (such as liotrix) and pure-T3 medications (INN: liothyronine). Levothyroxine
Levothyroxine
Sodium
Sodium
is usually the first course of treatment tried. Some patients feel they do better on desiccated thyroid hormones; however, this is based on anecdotal evidence and clinical trials have not shown any benefit over the biosynthetic forms.[4] Thyroid
Thyroid
tablets are reported to have different effects, which can be attributed to the difference in torsional angles surrounding the reactive site of the molecule.[5] Thyronamines
Thyronamines
have no medical usages yet, though their use has been proposed for controlled induction of hypothermia, which causes the brain to enter a protective cycle, useful in preventing damage during ischemic shock. Synthetic thyroxine was first successfully produced by Charles Robert Harington and George Barger
George Barger
in 1926. Formulations[edit] Today most patients are treated with levothyroxine, or a similar synthetic thyroid hormone.[6][7][8] Different polymorphs of the compound have different solubilities and potencies.[9] Additionally, natural thyroid hormone supplements from the dried thyroids of animals are still available.[8][10][11] Levothyroxine
Levothyroxine
contains T4 only and is therefore largely ineffective for patients unable to convert T4 to T3.[12] These patients may choose to take natural thyroid hormone, as it contains a mixture of T4 and T3,[8][13][14][15][16] or alternatively supplement with a synthetic T3 treatment.[17] In these cases, synthetic liothyronine is preferred due to the potential differences between the natural thyroid products. Some studies show that the mixed therapy is beneficial to all patients, but the addition of lyothyronine contains additional side effects and the medication should be evaluated on an individual basis.[18] Some natural thyroid hormone brands are FDA approved, but some are not.[19][20][21] Thyroid hormones are generally well tolerated.[7] Thyroid
Thyroid
hormones are usually not dangerous for pregnant women or nursing mothers, but should be given under a doctor's supervision. In fact, if a woman who is hypothyroid is left untreated, her baby is at a higher risk for birth defects. When pregnant, a woman with a low-functioning thyroid will also need to increase her dosage of thyroid hormone.[7] One exception is that thyroid hormones may aggravate heart conditions, especially in older patients; therefore, doctors may start these patients on a lower dose and work up to a larger one to avoid risk of heart attack.[8] Production[edit]

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Central[edit]

Synthesis of the thyroid hormones, as seen on an individual thyroid follicular cell:[22][page needed] - Thyroglobulin
Thyroglobulin
is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis. - Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I−) actively into the cell, which previously has crossed the endothelium by largely unknown mechanisms. - This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner. - In the colloid, iodide (I−) is oxidized to iodine (I0) by an enzyme called thyroid peroxidase. - Iodine
Iodine
(I0) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total containing approximately 120 tyrosyl residues). - In conjugation, adjacent tyrosyl residues are paired together. - Thyroglobulin
Thyroglobulin
re-enters the follicular cell by endocytosis. - Proteolysis
Proteolysis
by various proteases liberates thyroxine and triiodothyronine molecules - Efflux of thyroxine and triiodothyronine from follicular cells, which appears to be largely through monocarboxylate transporter (MCT) 8 and 10,[23][24] and entry into the blood.

Thyroid
Thyroid
hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland. The effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues). T3 is 3- to 5- fold more active than T4. Thyroxine
Thyroxine
(3,5,3',5'-tetraiodothyronine) is produced by follicular cells of the thyroid gland. It is produced as the precursor thyroglobulin (this is not the same as thyroxine-binding globulin (TBG)), which is cleaved by enzymes to produce active T4. The steps in this process are as follows:[22]

The Na+/I− symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodide ion. This is a secondary active transporter that utilises the concentration gradient of Na+ to move I− against its concentration gradient. I− is moved across the apical membrane into the colloid of the follicle. Thyroperoxidase
Thyroperoxidase
oxidizes two I− to form I2. Iodide is non-reactive, and only the more reactive iodine is required for the next step. The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid. The thyroglobulin was synthesised in the ER of the follicular cell and secreted into the colloid. Iodinated Thyroglobulin
Thyroglobulin
binds megalin for endocytosis back into cell. Thyroid-stimulating hormone
Thyroid-stimulating hormone
(TSH) released from the anterior pituitary (also known as the adenohypophysis) binds the TSH receptor (a Gs protein-coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid. The endocytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T4 from the iodinated thyroglobulin. The thyroid hormones cross the follicular cell membrane towards the blood vessels by an unknown mechanism.[22] Text books have stated that diffusion is the main means of transport,[25] but recent studies indicate that monocarboxylate transporter (MCT) 8 and 10 play major roles in the efflux of the thyroid hormones from the thyroid cells.[23][24]

Thyroglobulin
Thyroglobulin
(Tg) is a 660 kDa, dimeric protein produced by the follicular cells of the thyroid and used entirely within the thyroid gland.[citation needed] Thyroxine
Thyroxine
is produced by attaching iodine atoms to the ring structures of this protein's tyrosine residues; thyroxine (T4) contains four iodine atoms, while triiodothyronine (T3), otherwise identical to T4, has one less iodine atom per molecule. The thyroglobulin protein accounts for approximately half of the protein content of the thyroid gland.[citation needed] Each thyroglobulin molecule contains approximately 100-120 tyrosine residues, a small number of which (<20) are subject to iodination catalysed by thyroperoxidase.[26] The same enzyme then catalyses "coupling" of one modified tyrosine with another, via a free radical-mediated reaction, and when these iodinated bicyclic molecules are released by hydrolysis of the protein, T3 and T4 are the result.[citation needed] Therefore, each thyroglobulin protein molecule ultimately yields very small amounts of thyroid hormone (experimentally observed to be on the order of 5-6 molecules of either T4 or T3 per original molecule of thyroglobulin).[26] More specifically, the monoatomic, anionic form of iodine, iodide,

I

displaystyle I

—, is actively absorbed from the bloodstream by a process called iodide trapping.[citation needed] In this process, sodium is cotransported with iodide from the basolateral side of the membrane into the cell,[clarification needed] and then concentrated in the thyroid follicles to about thirty times its concentration in the blood.[citation needed] Then, in the first reaction catalysed by the enzyme thyroperoxidase, tyrosine residues in the protein thyroglobulin are iodinated on their phenol rings, at one or both of the positions ortho to the phenolic hydroxyl group, yielding monoiodotyrosine (MIT) and diiodotyrosine (DIT), respectively. This introduces 1-2 atoms of the element iodine, covalently bound, per tyrosine residue.[citation needed] The further coupling together of two fully iodinated tyrosine residues, also catalysed by thyroperoxidase, yields the peptidic (still peptide-bound) precursor of thyroxine, and coupling one molecule of MIT and one molecule of DIT yields the comparable precursor of triiodothyronine:[citation needed]

peptidic MIT + peptidic DIT → peptidic triiodothyronine (eventually released as triiodothyronine, T3) 2 peptidic DITs → peptidic thyroxine (eventually released as thyroxin, T4)

(Coupling of DIT to MIT in the opposite order yields a substance, r-T3, which is biologically inactive.[relevant? – discuss][citation needed]) Hydrolysis (cleavage to individual amino acids) of the modified protein by proteases then liberates T3 and T4, as well as the non-coupled tyrosine derivatives MIT and DIT.[citation needed] The hormones T4 and T3 are the biologically active agents central to metabolic regulation.[citation needed] Peripheral[edit] Thyroxine
Thyroxine
is believed to be a prohormone and a reservoir for the most active and main thyroid hormone T3.[27] T4 is converted as required in the tissues by iodothyronine deiodinase.[28] Deficiency of deiodinase can mimic hypothyroidism due to iodine deficiency.[29] T3 is more active than T4,[30] though it is present in less quantity than T4. Initiation of production in fetuses[edit] Thyrotropin-releasing hormone
Thyrotropin-releasing hormone
(TRH) is released from hypothalamus by 6 – 8 weeks, and thyroid-stimulating hormone (TSH) secretion from fetal pituitary is evident by 12 weeks of gestation, and fetal production of thyroxine (T4) reaches a clinically significant level at 18–20 weeks.[31] Fetal triiodothyronine (T3) remains low (less than 15 ng/dL) until 30 weeks of gestation, and increases to 50 ng/dL at term.[31] Fetal self-sufficiency of thyroid hormones protects the fetus against e.g. brain development abnormalities caused by maternal hypothyroidism.[32] Effect of iodine deficiency on thyroid hormone synthesis[edit]

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If there is a deficiency of dietary iodine, the thyroid will not be able to make thyroid hormone. The lack of thyroid hormone will lead to decreased negative feedback on the pituitary, leading to increased production of thyroid-stimulating hormone, which causes the thyroid to enlarge (the resulting medical condition is called endemic colloid goitre; see goitre). This has the effect of increasing the thyroid's ability to trap more iodide, compensating for the iodine deficiency and allowing it to produce adequate amounts of thyroid hormone. Circulation and transport[edit] Plasma transport[edit] Most of the thyroid hormone circulating in the blood is bound to transport proteins. Only a very small fraction of the circulating hormone is free (unbound) and biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.

Type Percent

bound to thyroxine-binding globulin (TBG) 70%

bound to transthyretin or "thyroxine-binding prealbumin" (TTR or TBPA) 10-15%

albumin 15-20%

unbound T4 (fT4) 0.03%

unbound T3 (fT3) 0.3%

Despite being lipophilic, T3 and T4 cross the cell membrane via carrier-mediated transport, which is ATP-dependent.[33] T1a and T0a are positively charged and do not cross the membrane; they are believed to function via the trace amine-associated receptor TAAR1 (TAR1, TA1), a G-protein-coupled receptor
G-protein-coupled receptor
located in the cell membrane. Another critical diagnostic tool is measurement of the amount of thyroid-stimulating hormone (TSH) that is present. Membrane transport[edit] Contrary to common belief, thyroid[34] hormones cannot traverse cell membranes in a passive manner like other lipophilic substances. The iodine in o-position makes the phenolic OH-group more acidic, resulting in a negative charge at physiological pH. However, at least 10 different active, energy-dependent and genetically-regulated iodothyronine transporters have been identified in humans. They guarantee that intracellular levels of thyroid hormones are higher than in blood plasma or interstitial fluids.[35] Intracellular transport[edit] Little is known about intracellular kinetics of thyroid hormones. However, recently it could be demonstrated that the crystallin CRYM binds 3,5,3′-triiodothyronine in vivo.[36] Mechanism of action[edit] Main article: Thyroid
Thyroid
hormone receptor The thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. These receptors, together with corepressor molecules, bind DNA regions called thyroid hormone response elements (TREs) near genes. This receptor-corepressor-DNA complex can block gene transcription. When triiodothyronine (T3) binds a receptor, it induces a conformational change in the receptor, displacing the corepressor from the complex. This leads to recruitment of coactivator proteins and RNA polymerase, activating transcription of the gene. [37] Although this general functional model has considerable experimental support, there remain many open questions. [38] Thyroxine, iodine and apoptosis[edit]

Amphibian
Amphibian
metamorphosis

Thyroxine
Thyroxine
and iodine stimulate the spectacular apoptosis of the cells of the larval gills, tail and fins in amphibian metamorphosis, and stimulate the evolution of their nervous system transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog. In fact, amphibian frog Xenopus laevis serves as an ideal model system for the study of the mechanisms of apoptosis.[39][40][41][42] Effects of triiodothyronine[edit] Effects of triiodothyronine (T3) which is the metabolically active form:

Increases cardiac output Increases heart rate Increases ventilation rate Increases basal metabolic rate Potentiates the effects of catecholamines (i.e. increases sympathetic activity) Potentiates brain development Thickens endometrium in females Increases catabolism of proteins and carbohydrates[43]

Measurement[edit] Further information: Thyroid
Thyroid
function tests Thyroxine
Thyroxine
and triiodothyronine can be measured as free thyroxine and free triiodothyronine, which are indicators of thyroxine and triiodothyronine activities in the body. They can also be measured as total thyroxine and total triiodothyronine, which also depend on the thyroxine and triiodothyronine that is bound to thyroxine-binding globulin. A related parameter is the free thyroxine index, which is total thyroxine multiplied by thyroid hormone uptake, which, in turn, is a measure of the unbound thyroxine-binding globulins.[44] Additionally, thyroid disorders can be detected prenatally using advanced imaging techniques and testing fetal hormone levels.[45] Related diseases[edit] Both excess and deficiency of thyroxine can cause disorders.

Hyperthyroidism
Hyperthyroidism
(an example is Graves Disease) is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men. Thyrotoxicosis is often used interchangeably with hyperthyroidism, but there are subtle differences. Although thyrotoxicosis also refers to an increase in circulating thyroid hormones, it can be caused by the intake of thyroxine tablets or by an over-active thyroid, whereas hyperthyroidism refers solely to an over-active thyroid. Hypothyroidism
Hypothyroidism
(an example is Hashimoto's thyroiditis) is the case where there is a deficiency of thyroxine, triiodothyronine, or both. Clinical depression
Clinical depression
can sometimes be caused by hypothyroidism.[46] Some research[47] has shown that T3 is found in the junctions of synapses, and regulates the amounts and activity of serotonin, norepinephrine, and γ-aminobutyric acid (GABA) in the brain. Hair loss can sometimes be attributed to a malfunction of T3 and T4. Normal hair growth cycle may be affected disrupting the hair growth.

Preterm births can suffer neurodevelopmental disorders due to lack of maternal thyroid hormones, at a time when their own thyroid is unable to meet their postnatal needs.[48] Also in normal pregnancies, adequate levels of maternal thyroid hormone are vital in order to ensure thyroid hormone availability for the fetus and its developing brain.[49] Congenital hypothyroidism occurs in every 1 in 1600–3400 newborns with most being born asymptomatic and developing related symptoms weeks after birth.[50] Anti-thyroid drugs[edit] Iodine
Iodine
uptake against a concentration gradient is mediated by a sodium-iodine symporter and is linked to a sodium-potassium ATPase. Perchlorate
Perchlorate
and thiocyanate are drugs that can compete with iodine at this point. Compounds such as goitrin, carbimazole, methimazole, propylthiouracil can reduce thyroid hormone production by interfering with iodine oxidation.[51] thiocyanides & perchlorates are used as ionic inhibitors in anti thyroid compounds See also[edit]

Goitre Graves-Basedow disease Hashimoto's thyroiditis Hormone Polar T3 syndrome Thyroid
Thyroid
gland Thyroid-stimulating hormone Thyronamines, metabolites of the thyroid hormones that act at the trace amine-associated receptor TAAR1
TAAR1
(TAR1)

References[edit]

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hormones as neurotransmitters". Thyroid. 6 (6): 639–47. doi:10.1089/thy.1996.6.639. PMID 9001201.  ^ Berbel, P; Navarro, D; Ausó, E; Varea, E; Rodríguez, AE; Ballesta, JJ; Salinas, M; Flores, E; Faura, CC; de Escobar, GM (2010). "Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity". Cerebral Cortex. 20 (6): 1462–75. doi:10.1093/cercor/bhp212. PMC 2871377 . PMID 19812240.  ^ Korevaar, TI; Muetzel, R; Medici, M; Chaker, L; Jaddoe, VW; de Rijke, YB; Steegers, EA; Visser, TJ; White, T; Tiemeier, H; Peeters, RP (2016). "Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study". The Lancet Diabetes & Endocrinology. 4 (1): 35–43. doi:10.1016/s2213-8587(15)00327-7. PMID 26497402.  ^ Szinnai, G (2014). "Genetics of normal and abnormal thyroid development in humans". Best Practice & Research Clinical Endocrinology & Metabolism. 28 (2): 133–150. doi:10.1016/j.beem.2013.08.005.  ^ Spiegel C, Bestetti GE, Rossi GL, Blum JW (September 1993). "Normal circulating triiodothyronine concentrations are maintained despite severe hypothyroidism in growing pigs fed rapeseed presscake meal". Journal of Nutrition. 123 (9): 1554–61. PMID 8360780. 

External links[edit]

Find TH response elements in DNA sequences. Triiodothyronine
Triiodothyronine
bound to proteins in the PDB Thyroxine
Thyroxine
bound to proteins in the PDB T4 at Lab Tests Online

Thyroid
Thyroid
hormone treatment in thyroid disease

Thyroid
Thyroid
Hormone
Hormone
Treatment Brochure by the American Thyroid
Thyroid
Association Elaborate article about the use of thyroid drugs Written by an MD Thyroid
Thyroid
Disease Manager Collection of elaborate medical articles on thyroid disease, including information on thyroid hormones

v t e

Hormones

Endocrine glands

Hypothalamic- pituitary

Hypothalamus

GnRH TRH Dopamine CRH GHRH Somatostatin
Somatostatin
(GHIH) MCH

Posterior pituitary

Oxytocin Vasopressin

Anterior pituitary

FSH LH TSH Prolactin POMC

CLIP ACTH MSH Endorphins Lipotropin

GH

Adrenal axis

Adrenal cortex

aldosterone cortisol cortisone DHEA DHEA-S androstenedione

Adrenal medulla

epinephrine norepinephrine

Thyroid

Thyroid
Thyroid
hormone

T3 T4

Calcitonin Thyroid
Thyroid
axis

Parathyroid

PTH

Gonadal axis

Testis

testosterone AMH inhibin

Ovary

estradiol progesterone activin and inhibin relaxin

Placenta

hCG HPL estrogen progesterone

Pancreas

glucagon insulin amylin somatostatin pancreatic polypeptide

Pineal gland

melatonin N,N-dimethyltryptamine 5-methoxy-N,N-dimethyltryptamine

Other

Thymus

Thymosins

Thymosin α1 Beta thymosins

Thymopoietin Thymulin

Digestive system

Stomach

gastrin ghrelin

Duodenum

CCK Incretins

GIP GLP-1

secretin motilin VIP

Ileum

enteroglucagon peptide YY

Liver/other

Insulin-like growth factor

IGF-1 IGF-2

Adipose tissue

leptin adiponectin resistin

Skeleton

Osteocalcin

Kidney

renin EPO calcitriol prostaglandin

Heart

Natriuretic peptide

ANP BNP

v t e

Thyroid
Thyroid
therapy (H03)

Thyroid
Thyroid
hormones

Levothyroxine# Liothyronine Liotrix Tiratricol Thyroid gland
Thyroid gland
preparations

Antithyroid preparations

Thyroid
Thyroid
peroxidase inhibitors (thioamide)

Thiouracils

Propylthiouracil# Methylthiouracil Benzylthiouracil

Sulfur-containing imidazole derivatives:

Carbimazole Methimazole

Block conversion of T4 to T3

Propylthiouracil# Ipodate

Sodium-iodide symporter inhibitor

Perchlorate
Perchlorate
(Potassium perchlorate) Pertechnetate
Pertechnetate
( Sodium
Sodium
pertechnetate)

Other

Diiodotyrosine Dibromotyrosine

#WHO-EM ‡Withdrawn from market Clinical trials:

†Phase III §Never to phase III

v t e

Thyroid
Thyroid
hormone receptor modulators

Receptor (ligands)

THR

Agonists: Dextrothyroxine DIMIT DITPA Eprotirome (KB-2115) KB-141 KB-2611 KB-130015 Levothyroxine Liothyronine Liotrix MB-07344 MB-07811 MGL-3196 (VIA-3196) Sobetirome (GC-1, GRX-431) Thyroxine Tiratricol
Tiratricol
(TRIAC) Triiodothyronine Thyroid
Thyroid
extract VK-0214 VK-2809 ZYT1

Antagonists: 1-850 NH3 Tetraiodothyroacetic acid (Tetrac)

Transporter (blockers)

NIS  

Inhibitors: Cyanogenic glycosides Perchlorates (e.g., potassium perchlorate) Pertechnetates (e.g., sodium pertechnetate) Thiocyanates

Enzyme (inhibitors)

TPO

Inhibitors: Benzylthiouracil Carbimazole Genistein Methimazole Methylthiouracil Propylthiouracil Thiouracil Thiourea

DIO

Inhibitors: Dexpropranolol Iopanoic acid Ipodate sodium
Ipodate sodium
(sodium iopodate) Propranolol Propylthiouracil

Others

Iodine Iodine-131 Selenium Thyroglobulin Tyrosine

See also: Receptor/signaling modulators Nuclear receptor modulators

v t e

Human trace amine-associated receptor ligands

TAAR1

Agonists

Endogenous†

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

Synthetic‡

Amphetamine DOB DOET 4-Hydroxyamphetamine Isoprenaline MDA (tenamfetamine) MDMA
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

EPPTB
EPPTB
(RO5212773)

TAAR2

Agonists‡

3-Iodothyronamine Phenethylamine Tyramine

Neutral antagonists

 

TAAR5

Agonists‡

Dimethylethylamine Trimethylamine

Neutral antagonists

 

Inverse agonists‡

3-Iodothyronamine

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

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

See also: Receptor/si

.