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Details

Stereochemistry ABSOLUTE
Molecular Formula C16H22N6O4.C4H6O6.H2O
Molecular Weight 530.4858
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROTIRELIN TARTRATE MONOHYDRATE

SMILES

O.O[C@H]([C@@H](O)C(O)=O)C(O)=O.NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@@H]3CCC(=O)N3

InChI

InChIKey=IMEQDWQCFHIYJB-LOMBACLASA-N
InChI=1S/C16H22N6O4.C4H6O6.H2O/c17-14(24)12-2-1-5-22(12)16(26)11(6-9-7-18-8-19-9)21-15(25)10-3-4-13(23)20-10;5-1(3(7)8)2(6)4(9)10;/h7-8,10-12H,1-6H2,(H2,17,24)(H,18,19)(H,20,23)(H,21,25);1-2,5-6H,(H,7,8)(H,9,10);1H2/t10-,11-,12-;1-,2-;/m01./s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C16H22N6O4
Molecular Weight 362.3837
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12683933

Protirelin is the pharmaceutically available synthetic analogue of the endogenous peptide thyrotropin-releasing hormone (TRH). It is a tri-peptide tropic hormone, released by the hypothalamus, which stimulates the release of Thyroid Stimulating Hormone (TSH) and prolactin from the anterior pituitary. Although not currently available in any FDA-approved product, protirelin is a component of the TRH Test where it is used to test the response of the anterior pituitary gland in conditions such as secondary hypothyroidism and acromegaly. TRH is indicated as an adjunctive agent in the diagnostic assessment of thyroid function. As an adjunct to other diagnostic procedures, testing with TRH (protirelin) may yield useful information in patients with pituitary or hypothalamic dysfunction. TRH is indicated as an adjunct to evaluate the effectiveness of thyrotropin suppression with a particular dose of T4 in patients with nodular or diffuse goiter. A normal TSH baseline value and a minimal difference between the 30 minute and baseline response to TRH injection would indicate adequate suppression of the pituitary secretion of TSH. TRH may be used, adjunctively, for adjustment of thyroid hormone dosage given to patients with primary hypothyroidism. A normal or slightly blunted TSH response, thirty minutes following TRH injection, would indicate adequate replacement therapy. Side effects have been reported in about 50% of the patients tested with TRH. Generally, the side effects are moor, have occurred promptly, and have persisted for only a few minutes following injection. Cardiovascular reactions: Marked changes in blood pressure, including both hypertension and hypotension with or without syncope, have been reported in a small number of patients. Endocrine reaction: Breast enlargement and leakage in lactating women for up to two or three days. Other reactions: Headaches, sometimes severe, and transient amaurosis in patients with pituitary tumors. Rarely, convulsions may occur in patients with predisposing conditions, e.g., epilepsy, brain damage. Nausea; urge to urinate; flushed sensation; light-headedness; bad taste in mouth; abdominal discomfort; and dry mouth. Less frequently reported were: Anxiety; sweating; tightness in the throat; pressure in the chest; tingling sensation; drowsiness; and allergic reactions. Pharmacologically, TRH increases the release of the thyroid stimulating hormone (TSH) from the anterior pituitary. Prolactin release is also increased. It has recently been observed that approximately 65% of acromegalic patients tested respond with a rise in circulating growth hormone levels; the clinical significance is as yet not clear. Following intravenous administration, the mean plasma half-life of protirelin in normal subjects is approximately five minutes. TSH levels rise rapidly and reach a peak at 20 to 30 minutes. The decline in TSH levels takes place more slowly, approaching baseline levels after approximately three hours.

CNS Activity

Curator's Comment: thyrotropin-releasing hormone molecule may slowly penetrate the blood-brain barrier Known to be CNS penetrant in guinea pig. Human data not available

Originator

Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/4982117

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Diagnostic
Thyrel TRH

Approved Use

Protirelin is used to test the response of the anterior pituitary gland in people who may have certain medical conditions involving the thyroid gland. Testing with this medicine may help to identify the problem or may ensure that the dose of medicine being used is correct.
Palliative
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Effects of acute prolactin manipulation on sexual drive and function in males.
2003 Dec
Thyrotropin-releasing hormone (protirelin) inhibits potassium-stimulated glutamate and aspartate release from hippocampal slices in vitro.
2005 Aug 23
Patents

Sample Use Guides

Adults: 500 μg. Doses between 200 and 500 μg have been used. 500 μg is considered the optimum dose to give the maximum response in the greatest number of patients. Doses greater than 500 μg are unlikely to elicit a greater TSH response. Children age 6 to 16 years: 7 μg/kg body weight up to a dose of 500 μg. Infants and children up to 6 years: Experience is limited in this age group; doses of 7μg/kg have been administered.
Route of Administration: Intravenous
In Vitro Use Guide
Curator's Comment: The effects of thyrotropin-releasing hormone (TRH) on growth hormone (GH) and gonadotropin (GtH) release, and the influences of somatostatin (SRIF), the dopamine agonist apomorphine (APO) and extracellular calcium on basal and TRH-induced GH release were examined using an in vitro perifusion system for pituitary fragments of common carp (Cyprinus carpio). Five minute pulses of different dosages of TRH stimulated a rapid and dose-dependent increase in GH release from the perifused pituitary fragments with an ED50 of 9.7 ± 2.3 nM. TRH was ineffective on GtH release.
Unknown
Substance Class Chemical
Created
by admin
on Sat Dec 16 05:55:18 GMT 2023
Edited
by admin
on Sat Dec 16 05:55:18 GMT 2023
Record UNII
1N3H4TJE79
Record Status Validated (UNII)
Record Version
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Name Type Language
PROTIRELIN TARTRATE MONOHYDRATE
Common Name English
L-PROLINAMIDE, 5-OXO-L-PROLYL-L-HISTIDYL-, (R-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (1:1), MONOHYDRATE
Common Name English
L-PROLINAMIDE, 5-OXO-L-PROLYL-L-HISTIDYL-, (2R,3R)-2,3-DIHYDROXYBUTANEDIOATE (1:1), MONOHYDRATE
Common Name English
PROTIRELIN TARTRATE HYDRATE [JAN]
Common Name English
Protirelin tartrate monohydrate [WHO-DD]
Common Name English
PROTIRELIN TARTRATE HYDRATE
JAN  
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID20204821
Created by admin on Sat Dec 16 05:55:18 GMT 2023 , Edited by admin on Sat Dec 16 05:55:18 GMT 2023
PRIMARY
FDA UNII
1N3H4TJE79
Created by admin on Sat Dec 16 05:55:18 GMT 2023 , Edited by admin on Sat Dec 16 05:55:18 GMT 2023
PRIMARY
CAS
56267-12-0
Created by admin on Sat Dec 16 05:55:18 GMT 2023 , Edited by admin on Sat Dec 16 05:55:18 GMT 2023
PRIMARY
PUBCHEM
5282469
Created by admin on Sat Dec 16 05:55:18 GMT 2023 , Edited by admin on Sat Dec 16 05:55:18 GMT 2023
PRIMARY
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ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
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ACTIVE MOIETY