Iopanoic acid

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Iopanoic acid
Iopanoic acid.png
Clinical data
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ATC code
Identifiers
  • (RS)-2-[(3-Amino-2,4,6-triiodophenyl)methyl]butanoic acid
CAS Number
PubChem CID
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KEGG
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Chemical and physical data
Formula C11H12I3NO2
Molar mass 570.935 g·mol−1
3D model (JSmol)
Melting point 162–163 °C (324–325 °F)
  • CCC(CC1=C(C(=C(C=C1I)I)N)I)C(=O)O
  • InChI=1S/C11H12I3NO2/c1-2-5(11(16)17)3-6-7(12)4-8(13)10(15)9(6)14/h4-5H,2-3,15H2,1H3,(H,16,17)
  • Key:OIRFJRBSRORBCM-UHFFFAOYSA-N

Iopanoic acid is an iodine-containing radiocontrast medium used in cholecystography. Both iopanoic acid and ipodate sodium are potent inhibitors of thyroid hormone release from thyroid gland, as well as of peripheral conversion of thyroxine (T4) to triiodothyronine (T3). These compounds inhibit 5'deiodinase (5'DID-1 and 5'DID-2) enzymes, which catalyse T4-T3 conversion in the thyroid cell, liver, kidney, skeletal muscle, heart, brain, pituitary. This accounts for the dramatic improvement in both subjective and objective symptoms of hyperthyroidism, particularly when they are used as an adjunctive therapy with thioamides (propylthiouracil, carbimazole). They can be used in the treatment of patients with severe thyrotoxicosis (thyroid storm) and significant morbidity (e.g., myocardial infarction, or stroke) for rapid control of elevated plasma triiodothyronine concentrations. The use of iopanoic acid for treatment of thyrotoxicosis has been discontinued in the United States.

In addition to inhibiting deiodinase enzymes, iopanoic acid is also a substrate of type 1 deiodinase. Iopanoic acid underwent monodeiodination in the presence of type 1 deiodinase in a microsomal mouse liver preparation. [1]

Related Research Articles

<span class="mw-page-title-main">Hyperthyroidism</span> Thyroid gland disease that involves an overproduction of thyroid hormone

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon but life-threatening complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature; this often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

<span class="mw-page-title-main">Iodothyronine deiodinase</span> Class of enzymes

Iodothyronine deiodinases (EC 1.21.99.4 and EC 1.21.99.3) are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine (T4), the precursor of 3,5,3'-triiodothyronine (T3) is transformed into T3 by deiodinase activity. T3, through binding a nuclear thyroid hormone receptor, influences the expression of genes in practically every vertebrate cell. Iodothyronine deiodinases are unusual in that these enzymes contain selenium, in the form of an otherwise rare amino acid selenocysteine.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

<span class="mw-page-title-main">Triiodothyronine</span> Chemical compound

Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.

<span class="mw-page-title-main">Levothyroxine</span> Thyroid hormone

Levothyroxine, also known as L-thyroxine, is a synthetic form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken orally (by mouth) or given by intravenous injection. Levothyroxine has a half-life of 7.5 days when taken daily, so about six weeks is required for it to reach a steady level in the blood.

<span class="mw-page-title-main">Propylthiouracil</span> Medication used to treat hyperthyroidism

Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. Otherwise it is typically only used when methimazole, surgery, and radioactive iodine is not possible. It is taken by mouth.

<span class="mw-page-title-main">Thioamide</span> Class of organic compounds

A thioamide is a functional group with the general structure R1−C(=S)−NR2R3, where R1, R2 and R3 are any groups. Analogous to amides, thioamides exhibit greater multiple bond character along the C-N bond, resulting in a larger rotational barrier.

Thyroid storm is a rare but severe and life-threatening complication of hyperthyroidism. It occurs when overactive thyroid activity leads to hypermetabolism, the end result being death from cardiac arrest or multiple organ failure.

Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of the thyroid. TFTs may be requested if a patient is thought to suffer from hyperthyroidism or hypothyroidism, or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as atrial fibrillation and anxiety disorder.

Goitrogens are substances that disrupt the production of thyroid hormones. This triggers the pituitary to release thyroid-stimulating hormone (TSH), which then promotes the growth of thyroid tissue, eventually leading to goiter.

<span class="mw-page-title-main">Thyroxine 5-deiodinase</span> Protein-coding gene in the species Homo sapiens

Thyroxine 5-deiodinase also known as type III iodothyronine deiodinase (EC number 1.21.99.3) is an enzyme that in humans is encoded by the DIO3 gene. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Hypothalamic–pituitary–thyroid axis</span> Part of the neuroendocrine system

The hypothalamic–pituitary–thyroid axis is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress.

<span class="mw-page-title-main">Reverse triiodothyronine</span> Chemical compound

Reverse triiodothyronine (3,3′,5′-triiodothyronine, reverse T3, or rT3) is an isomer of triiodothyronine (3,5,3′ triiodothyronine, T3).

An antithyroid agent is a hormone inhibitor acting upon thyroid hormones.

Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from allostatic responses of hypothalamus-pituitary-thyroid feedback control, dyshomeostatic disorders, drug interferences, and impaired assay characteristics in critical illness.

<span class="mw-page-title-main">Allan–Herndon–Dudley syndrome</span> Medical condition

Allan–Herndon–Dudley syndrome is a rare X-linked inherited disorder of brain development that causes both moderate to severe intellectual disability and problems with speech and movement.

<span class="mw-page-title-main">Thyroid hormones</span> Hormones produced by the thyroid gland

Thyroid hormones are any hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine, derived from food. 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.

Organoiodine chemistry is the study of the synthesis and properties of organoiodine compounds, or organoiodides, organic compounds that contain one or more carbon–iodine bonds. They occur widely in organic chemistry, but are relatively rare in nature. The thyroxine hormones are organoiodine compounds that are required for health and the reason for government-mandated iodization of salt.

Deiodinase (monodeiodinase) is a peroxidase enzyme that is involved in the activation or deactivation of thyroid hormones.

The sum activity of peripheral deiodinases is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. It is assumed to reflect the activity of deiodinases outside the central nervous system and other isolated compartments. GD is therefore expected to reflect predominantly the activity of type I deiodinase.

References

  1. Renko K, Hoefig CS, Hiller F, Schomburg L, Köhrle J (May 2012). "Identification of iopanoic acid as substrate of type 1 deiodinase by a novel nonradioactive iodide-release assay". Endocrinology. 153 (5): 2506–13. doi: 10.1210/en.2011-1863 . PMID   22434082.