Corticorelin

Last updated
Corticorelin
Clinical data
AHFS/Drugs.com International Drug Names
ATC code
Pharmacokinetic data
Elimination half-life 9 minutes
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C208H344N60O63S2
Molar mass 4757.52 g·mol−1
3D model (JSmol)
  • [H]/N=C(\N)/NCCC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCN/C(=N/[H])/N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN/C(=N/[H])/N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]4CCCN4C(=O)[C@@H]5CCCN5C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N
  • InChI=1S/C208H344N60O63S2/c1-30-106(20)161(165(215)291)263-202(328)163(108(22)32-3)264-184(310)129(58-67-157(285)286)243-182(308)131(70-78-333-29)246-187(313)134(80-99(6)7)250-176(302)118(45-36-37-71-209)237-174(300)120(47-39-73-225-207(218)219)239-194(320)143(89-152(214)276)256-197(323)145(94-270)260-193(319)141(87-115-91-222-96-227-115)248-169(295)112(26)230-172(298)122(51-60-149(211)273)240-177(303)123(52-61-150(212)274)234-168(294)111(25)232-185(311)133(79-98(4)5)249-181(307)124(53-62-151(213)275)241-178(304)125(54-63-153(277)278)235-167(293)110(24)229-171(297)119(46-38-72-224-206(216)217)233-166(292)109(23)231-173(299)130(69-77-332-28)245-179(305)127(56-65-155(281)282)244-188(314)138(84-103(14)15)258-200(326)160(105(18)19)262-183(309)128(57-66-156(283)284)242-175(301)121(48-40-74-226-208(220)221)238-186(312)135(81-100(8)9)251-189(315)136(82-101(10)11)252-192(318)142(88-116-92-223-97-228-116)255-191(317)140(86-114-43-34-33-35-44-114)259-203(329)164(113(27)272)266-196(322)139(85-104(16)17)253-195(321)144(90-159(289)290)257-190(316)137(83-102(12)13)254-198(324)146(95-271)261-201(327)162(107(21)31-2)265-199(325)147-49-41-75-267(147)205(331)148-50-42-76-268(148)204(330)132(59-68-158(287)288)247-180(306)126(55-64-154(279)280)236-170(296)117(210)93-269/h33-35,43-44,91-92,96-113,117-148,160-164,269-272H,30-32,36-42,45-90,93-95,209-210H2,1-29H3,(H2,211,273)(H2,212,274)(H2,213,275)(H2,214,276)(H2,215,291)(H,222,227)(H,223,228)(H,229,297)(H,230,298)(H,231,299)(H,232,311)(H,233,292)(H,234,294)(H,235,293)(H,236,296)(H,237,300)(H,238,312)(H,239,320)(H,240,303)(H,241,304)(H,242,301)(H,243,308)(H,244,314)(H,245,305)(H,246,313)(H,247,306)(H,248,295)(H,249,307)(H,250,302)(H,251,315)(H,252,318)(H,253,321)(H,254,324)(H,255,317)(H,256,323)(H,257,316)(H,258,326)(H,259,329)(H,260,319)(H,261,327)(H,262,309)(H,263,328)(H,264,310)(H,265,325)(H,266,322)(H,277,278)(H,279,280)(H,281,282)(H,283,284)(H,285,286)(H,287,288)(H,289,290)(H4,216,217,224)(H4,218,219,225)(H4,220,221,226)/t106-,107-,108-,109-,110-,111-,112-,113+,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,144-,145-,146-,147-,148-,160-,161-,162-,163-,164-/m0/s1
  • Key:GBONBLHJMVUBSJ-FAUHKOHMSA-N
   (verify)

Corticorelin (INN, trade name Xerecept) is a diagnostic agent. It is a synthetic form of human corticotropin-releasing hormone (hCRH). [1]

Contents

Medical uses

The corticorelin stimulation test helps to differentiate between the causes for adrenocorticotropic hormone (ACTH)-dependent hypercortisolism. It is used to distinguish a pituitary source of excessive ACTH secretion from a different source.

Side effects

The most common side effects (in 1% to 10% of patients) are transient dysosmia and dysgeusia (distortion of the sense of smell and taste), as well as a sensation of warmth. About 0.1 to 1% of patients experience hypersensitivity, hypotension (lowering of blood pressure), tachycardia (increased heart rate), flush, dyspnoea (breathing difficulties), a cold sensation in the throat, the urge to urinate, and dizziness. Pituitary apoplexy has been reported in patients with pituitary tumours. [2]

Interactions

The effects of corticorelin are reduced by corticosteroids, antihistamines, antiserotonergics and oxytocin. They are amplified by vasopressin and its analogues. [2]

See also

Related Research Articles

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the cortex and medulla of the adrenal gland, respectively. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Cushing's syndrome</span> Symptoms from excessive exposure to glucocorticoids such as cortisol

Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face due to facial plethora, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

<span class="mw-page-title-main">Corticotropin-releasing hormone</span> Mammalian protein found in Homo sapiens

Corticotropin-releasing hormone (CRH) is a peptide hormone involved in stress responses. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the CRH gene. Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis.

<span class="mw-page-title-main">Hypothalamic–pituitary–adrenal axis</span> Set of physiological feedback interactions

The hypothalamic–pituitary–adrenal axis is a complex set of direct influences and feedback interactions among three components: the hypothalamus, the pituitary gland, and the adrenal glands. These organs and their interactions constitute the HPA axis.

<span class="mw-page-title-main">Anterior pituitary</span> Anterior lobe of the pituitary gland

A major organ of the endocrine system, the anterior pituitary is the glandular, anterior lobe that together with the posterior lobe makes up the pituitary gland (hypophysis). The anterior pituitary regulates several physiological processes, including stress, growth, reproduction, and lactation. Proper functioning of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels.

<span class="mw-page-title-main">Cortisol</span> Human natural glucocorticoid hormone

Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.

Cushing's disease is one cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary. This is most often as a result of a pituitary adenoma or due to excess production of hypothalamus CRH that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome, when excluding Cushing's syndrome from exogenously administered corticosteroids. The equine version of this disease is Pituitary pars intermedia dysfunction.

<span class="mw-page-title-main">Adrenal insufficiency</span> Medical condition

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands, also referred to as adrenal cortex normally secretes glucocorticoids, mineralocorticoids, and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes to organ failure and shock. An adrenal crisis may occur if the body is subjected to stress, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow.

Corticotropes are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response.

<span class="mw-page-title-main">Hypopituitarism</span> Medical condition

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism is used.

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

Metyrapone, sold under the brand name Metopirone, is a medication which is used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism).

<span class="mw-page-title-main">Dexamethasone suppression test</span> Medical test

The dexamethasone suppression test (DST) is used to assess adrenal gland function by measuring how cortisol levels change in response to oral doses or an injection of dexamethasone. It is typically used to diagnose Cushing's syndrome.

In humans and other animals, the adrenocortical hormones are hormones produced by the adrenal cortex, the outer region of the adrenal gland. These polycyclic steroid hormones have a variety of roles that are crucial for the body’s response to stress, and they also regulate other functions in the body. Threats to homeostasis, such as injury, chemical imbalances, infection, or psychological stress, can initiate a stress response. Examples of adrenocortical hormones that are involved in the stress response are aldosterone and cortisol. These hormones also function in regulating the conservation of water by the kidneys and glucose metabolism, respectively.

An insulin tolerance test (ITT) is a medical diagnostic procedure during which insulin is injected into a patient's vein, after which blood glucose is measured at regular intervals. This procedure is performed to assess pituitary function, adrenal function, insulin sensitivity, and sometimes for other purposes. An ITT is usually ordered and interpreted by endocrinologists.

The ACTH test is a medical test usually requested and interpreted by endocrinologists to assess the functioning of the adrenal glands' stress response by measuring the adrenal response to adrenocorticotropic hormone or another corticotropic agent such as tetracosactide or alsactide (Synchrodyn). ACTH is a hormone produced in the anterior pituitary gland that stimulates the adrenal glands to release cortisol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and aldosterone.

Non-tropic hormones are hormones that directly stimulate target cells to induce effects. This differs from the tropic hormones, which act on another endocrine gland. Non-tropic hormones are those that act directly on targeted tissues or cells, and not on other endocrine gland to stimulate release of other hormones. Many hormones act in a chain reaction. Tropic hormones usually act in the beginning of the reaction stimulating other endocrine gland to eventually release non-tropic hormones. These are the ones that act in the end of the chain reaction on other cells that are not part of other endocrine gland. The Hypothalamic-pituitary-adrenal axis is a perfect example of this chain reaction. The reaction begins in the hypothalamus with a release of corticotropin-releasing hormone/factor. This stimulates the anterior pituitary and causes it to release Adrenocorticotropic hormone to the adrenal glands. Lastly, cortisol (non-tropic) is secreted from the adrenal glands and goes into the bloodstream where it can have more widespread effects on organs and tissues. Since cortisol is what finally reaches other tissues in the body, it is a non-tropic hormone. CRH and ACTH are tropic hormones because they act on the anterior pituitary gland and adrenal glands, respectively, both of which are endocrine glands. Non-tropic hormones are thus often the last piece of a larger process and chain of hormone secretion. Both tropic and non-tropic hormones are necessary for proper endocrine function. For example, if ACTH is inhibited, cortisol can no longer be released because the chain reaction has been interrupted. Some examples of non-tropic hormones are:

Critical illness–related corticosteroid insufficiency is a form of adrenal insufficiency in critically ill patients who have blood corticosteroid levels which are inadequate for the severe stress response they experience. Combined with decreased glucocorticoid receptor sensitivity and tissue response to corticosteroids, this adrenal insufficiency constitutes a negative prognostic factor for intensive care patients.

Hypoadrenocorticism in dogs, or, as it is known in people, Addison's disease, is an endocrine system disorder that occurs when the adrenal glands fail to produce enough hormones for normal function. The adrenal glands secrete glucocorticoids such as cortisol and mineralocorticoids such as aldosterone; when proper amounts of these are not produced, the metabolic and electrolyte balance is upset. Mineralocorticoids control the amount of potassium, sodium, and water in the body. Hypoadrenocorticism is fatal if left untreated.

<span class="mw-page-title-main">Pituitary pars intermedia dysfunction</span>

Pituitary pars intermedia dysfunction (PPID), or equine Cushing's disease, is an endocrine disease affecting the pituitary gland of horses. It is most commonly seen in older animals, and is classically associated with the formation of a long, wavy coat (hirsutism) and chronic laminitis.

<span class="mw-page-title-main">Adrenocorticotropic hormone (medication)</span> Chemical compound

Adrenocorticotropic hormone is used as a medication and as diagnostic agent in the ACTH stimulation test.

References

  1. Andoh K, Kimura T, Saeki I, et al. (June 1994). "General pharmacological properties of the human corticotropin-releasing hormone corticorelin (human)". Arzneimittelforschung. 44 (6): 715–26. PMID   8053970.
  2. 1 2 Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 2018.