ARGININE CITRATE

First approved in 1957

Details

Stereochemistry	ABSOLUTE
Molecular Formula	3C6H14N4O2.C6H8O7
Molecular Weight	714.7264
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@@H](CCCNC(N)=N)C(O)=O.N[C@@H](CCCNC(N)=N)C(O)=O.N[C@@H](CCCNC(N)=N)C(O)=O.OC(=O)CC(O)(CC(O)=O)C(O)=O

InChI

InChIKey=IHOWSFVYYZTGSY-FOIRCHMTSA-N

InChI=1S/3C6H14N4O2.C6H8O7/c3*7-4(5(11)12)2-1-3-10-6(8)9;7-3(8)1-6(13,5(11)12)2-4(9)10/h3*4H,1-3,7H2,(H,11,12)(H4,8,9,10);13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t3*4-;/m000./s1

HIDE SMILES / InChI

Molecular Formula	C6H14N4O2
Molecular Weight	174.201
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C6H8O7
Molecular Weight	192.1235
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugs.com/npp/l-arginine.html | http://www.webmd.com/diet/supplement-guide-l-arginine#1

L-arginine is a nonessential amino acid that may play an important role in the treatment of cardiovascular disease due to its antiatherogenic, anti-ischemic, antiplatelet, and antithrombotic properties. It has been promoted as a growth stimulant and as a treatment for erectile dysfunction in men. L-arginine is a nonessential amino acid that may play an important role in the treatment of heart disease due to its block arterial plaque buildup, blood clots, platelet clumping, and to increase blood flow through the coronary artery. L-arginine is commonly sold as a health supplement claiming to improve vascular health and treat erectile dysfunction in men. L-arginine, which is promoted as a human growth stimulant, has also been used in bodybuilding. In the 1800s, it was first isolated from animal horn.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
G-protein coupled receptor family C group 6 member A 22 Target ID: Q5T6X5 Gene ID: 222545.0 Gene Symbol: GPRC6A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15576628	Agonist 2678		44.1 µM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Panhypopituitarism 13 Sources: http://labeling.pfizer.com/ShowLabeling.aspx?id=642	Diagnostic	Approved 8429	R-GENE 10 Approved Use R-Gene 10 is indicated as an intravenous stimulant to the pituitary for the release of human growth hormone in patients where the measurement of pituitary reserve for HGH can be of diagnostic usefulness. It can be used as a diagnostic aid in such conditions as panhypopituitarism, pituitary dwarfism, chromophobe adenoma, postsurgical craniopharyngioma, hypophysectomy, pituitary trauma, acromegaly, gigantism and problems of growth and stature. If the insulin hypoglycemia test has indicated a deficiency of pituitary reserve for HGH, a test with R-Gene 10 is advisable to confirm the negative response. This can be done after a waiting period of one day. As patients may not respond to R-Gene 10 (Arginine Hydrochloride Injection, USP) during the first test, the unresponsive patient should be tested again to confirm the negative result. A second test can be performed after a waiting period of one day. Some patients who respond to R-Gene 10 do not respond to insulin and vice versa. The rate of false positive responses for R-Gene 10 is approximately 32%, and the rate of false negatives is approximately 27%. Launch Date 1973
Pituitary dwarfism 13 Sources: http://labeling.pfizer.com/ShowLabeling.aspx?id=642	Diagnostic	Approved 8429	R-GENE 10 Approved Use R-Gene 10 is indicated as an intravenous stimulant to the pituitary for the release of human growth hormone in patients where the measurement of pituitary reserve for HGH can be of diagnostic usefulness. It can be used as a diagnostic aid in such conditions as panhypopituitarism, pituitary dwarfism, chromophobe adenoma, postsurgical craniopharyngioma, hypophysectomy, pituitary trauma, acromegaly, gigantism and problems of growth and stature. If the insulin hypoglycemia test has indicated a deficiency of pituitary reserve for HGH, a test with R-Gene 10 is advisable to confirm the negative response. This can be done after a waiting period of one day. As patients may not respond to R-Gene 10 (Arginine Hydrochloride Injection, USP) during the first test, the unresponsive patient should be tested again to confirm the negative result. A second test can be performed after a waiting period of one day. Some patients who respond to R-Gene 10 do not respond to insulin and vice versa. The rate of false positive responses for R-Gene 10 is approximately 32%, and the rate of false negatives is approximately 27%. Launch Date 1973
Acromegaly 21 Sources: http://labeling.pfizer.com/ShowLabeling.aspx?id=642	Diagnostic	Approved 8429	R-GENE 10 Approved Use R-Gene 10 is indicated as an intravenous stimulant to the pituitary for the release of human growth hormone in patients where the measurement of pituitary reserve for HGH can be of diagnostic usefulness. It can be used as a diagnostic aid in such conditions as panhypopituitarism, pituitary dwarfism, chromophobe adenoma, postsurgical craniopharyngioma, hypophysectomy, pituitary trauma, acromegaly, gigantism and problems of growth and stature. If the insulin hypoglycemia test has indicated a deficiency of pituitary reserve for HGH, a test with R-Gene 10 is advisable to confirm the negative response. This can be done after a waiting period of one day. As patients may not respond to R-Gene 10 (Arginine Hydrochloride Injection, USP) during the first test, the unresponsive patient should be tested again to confirm the negative result. A second test can be performed after a waiting period of one day. Some patients who respond to R-Gene 10 do not respond to insulin and vice versa. The rate of false positive responses for R-Gene 10 is approximately 32%, and the rate of false negatives is approximately 27%. Launch Date 1973
Gigantism 13 Sources: https://www.drugs.com/dosage/r-gene-10.html http://labeling.pfizer.com/ShowLabeling.aspx?id=642	Diagnostic	Approved 8429	R-GENE 10 Approved Use R-Gene 10 is indicated as an intravenous stimulant to the pituitary for the release of human growth hormone in patients where the measurement of pituitary reserve for HGH can be of diagnostic usefulness. It can be used as a diagnostic aid in such conditions as panhypopituitarism, pituitary dwarfism, chromophobe adenoma, postsurgical craniopharyngioma, hypophysectomy, pituitary trauma, acromegaly, gigantism and problems of growth and stature. If the insulin hypoglycemia test has indicated a deficiency of pituitary reserve for HGH, a test with R-Gene 10 is advisable to confirm the negative response. This can be done after a waiting period of one day. As patients may not respond to R-Gene 10 (Arginine Hydrochloride Injection, USP) during the first test, the unresponsive patient should be tested again to confirm the negative result. A second test can be performed after a waiting period of one day. Some patients who respond to R-Gene 10 do not respond to insulin and vice versa. The rate of false positive responses for R-Gene 10 is approximately 32%, and the rate of false negatives is approximately 27%. Launch Date 1973
Type 2 diabetes mellitus 259 Sources: https://clinicaltrials.gov/ct2/show/NCT00917449	Preventing	Phase III 656	Unknown Approved Use Unknown
Preeclampsia 85 Sources: https://clinicaltrials.gov/ct2/show/NCT02363348	Preventing	Phase III 656	Unknown Approved Use Unknown
Hypertension 567 Sources: https://clinicaltrials.gov/ct2/show/NCT02894723	Primary	Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
310 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	6 g single, oral dose: 6 g route of administration: Oral experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
6219 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	30 g single, intravenous dose: 30 g route of administration: Intravenous experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
882 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	6 g single, intravenous dose: 6 g route of administration: Intravenous experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Analyte	Population
24788 M × min EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	6 g single, oral dose: 6 g route of administration: Oral experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
265435 M × min EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	30 g single, intravenous dose: 30 g route of administration: Intravenous experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
38223 M × min EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	6 g single, intravenous dose: 6 g route of administration: Intravenous experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
77.5 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	6 g single, oral dose: 6 g route of administration: Oral experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
41.6 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	30 g single, intravenous dose: 30 g route of administration: Intravenous experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
59.6 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873701/	6 g single, intravenous dose: 6 g route of administration: Intravenous experiment type: SINGLE co-administered:	ARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
100% EXPERIMENT https://www.jci.org/articles/view/103568			ARGININE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
3.9 g/kg single, intravenous Accidental dose Dose: 3.9 g/kg Route: intravenous Route: single Dose: 3.9 g/kg Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621	unhealthy, 1.75 n = 1 Health Status: unhealthy Condition: Short stature Age Group: 1.75 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621	Disc. AE: Cardiopulmonary arrest, Metabolic acidosis... AEs leading to discontinuation/dose reduction: Cardiopulmonary arrest Metabolic acidosis (acute) Hyponatremia (severe) Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621
200 mg/kg 3 times / day multiple, oral Highest studied dose Dose: 200 mg/kg, 3 times / day Route: oral Route: multiple Dose: 200 mg/kg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15640324 Page: p.63	unhealthy, 24 n = 11 Health Status: unhealthy Condition: Cystic fibrosis Age Group: 24 Sex: M+F Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/15640324 Page: p.63	Sources: https://pubmed.ncbi.nlm.nih.gov/15640324 Page: p.63
15 g 2 times / day multiple, oral Studied dose Dose: 15 g, 2 times / day Route: oral Route: multiple Dose: 15 g, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29858688 Page: p.1	healthy, 34 ± 2.6 n = 12 Health Status: healthy Condition: Dietary supplementation Age Group: 34 ± 2.6 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/29858688 Page: p.1	Sources: https://pubmed.ncbi.nlm.nih.gov/29858688 Page: p.1
7 g 3 times / day multiple, oral Studied dose Dose: 7 g, 3 times / day Route: oral Route: multiple Dose: 7 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9918901 Page: p.200	unhealthy, 43± 16 n = 10 Health Status: unhealthy Condition: Hypercholesterolaemia Age Group: 43± 16 Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/9918901 Page: p.200	DLT: Gastrointestinal discomfort... Dose limiting toxicities: Gastrointestinal discomfort (20%) Sources: https://pubmed.ncbi.nlm.nih.gov/9918901 Page: p.200

AEs

AE	Significance	Dose	Population
Cardiopulmonary arrest	Disc. AE	3.9 g/kg single, intravenous Accidental dose Dose: 3.9 g/kg Route: intravenous Route: single Dose: 3.9 g/kg Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621	unhealthy, 1.75 n = 1 Health Status: unhealthy Condition: Short stature Age Group: 1.75 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621
Metabolic acidosis	acute Disc. AE	3.9 g/kg single, intravenous Accidental dose Dose: 3.9 g/kg Route: intravenous Route: single Dose: 3.9 g/kg Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621	unhealthy, 1.75 n = 1 Health Status: unhealthy Condition: Short stature Age Group: 1.75 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621
Hyponatremia	severe Disc. AE	3.9 g/kg single, intravenous Accidental dose Dose: 3.9 g/kg Route: intravenous Route: single Dose: 3.9 g/kg Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621	unhealthy, 1.75 n = 1 Health Status: unhealthy Condition: Short stature Age Group: 1.75 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/9365430/ Page: p.621
Gastrointestinal discomfort	20% DLT	7 g 3 times / day multiple, oral Studied dose Dose: 7 g, 3 times / day Route: oral Route: multiple Dose: 7 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9918901 Page: p.200	unhealthy, 43± 16 n = 10 Health Status: unhealthy Condition: Hypercholesterolaemia Age Group: 43± 16 Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/9918901 Page: p.200

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:29016	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:29016
ChemicalBook	CB0693158	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0693158
MolPort	MolPort-001-779-889	https://www.molport.com/shop/molecule-link/MolPort-001-779-889
MolPort	MolPort-006-118-537	https://www.molport.com/shop/molecule-link/MolPort-006-118-537
eMolecules	10311512	https://www.emolecules.com/cgi-bin/more?vid=10311512
eMolecules	478568	https://www.emolecules.com/cgi-bin/more?vid=478568

PubMed

Title	Date	PubMed
Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans.	2000 Dec	11113071
Two novel mutations (Y141H; C214Y) and previously published mutation (R142W) in the RDS-peripherin gene in autosomal dominant macular dystrophies in Spanish families.	2001	11139263
A rare case of complete human erythrocyte AMP deaminase deficiency due to two novel missense mutations in AMPD3.	2001	11139257
Optimization of experimental conditions for RNA-based sequencing of MLH1 and MSH2 genes.	2001	11139242
Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies.	2001	11139241
The dialytic failure of the peritoneal membrane.	2001	11125567
Hemodialysis techniques and advanced glycation end products.	2001	11125561
AGE in micro- and macroangiopathy.	2001	11125555
Signal-binding specificity of the mu4 subunit of the adaptor protein complex AP-4.	2001 Apr 20	11139587
Nucleocytoplasmic shuttling of heterodimeric splicing factor U2AF.	2001 Apr 20	11118443
An intrahelical salt bridge within the trigger site stabilizes the GCN4 leucine zipper.	2001 Apr 27	11134036
Fructose-6-phosphate aldolase is a novel class I aldolase from Escherichia coli and is related to a novel group of bacterial transaldolases.	2001 Apr 6	11120740
Dose response of arginine vasopressin to the CCK-B agonist pentagastrin.	2001 Feb	11120398
Abnormalities in response to vasopressin infusion in chronic fatigue syndrome.	2001 Feb	11087963
Kinetics of CO and NO ligation with the Cys(331)-->Ala mutant of neuronal nitric-oxide synthase.	2001 Feb 16	11067850
Amino acid residues outside of the pore region contribute to N-type calcium channel permeation.	2001 Feb 23	11120735
The nutritional management of urea cycle disorders.	2001 Jan	11148548
Current strategies for the management of neonatal urea cycle disorders.	2001 Jan	11148547
Prevention of diabetes for up to 13 years by autoislet transplantation after pancreatectomy for chronic pancreatitis.	2001 Jan	11147793
Effect of AVT antisense oligodeoxynucleotides on AVT release induced by hypertonic stimulation in chicks.	2001 Jan	11137447
Regulation of potassium channel Kir 1.1 (ROMK) abundance in the thick ascending limb of Henle's loop.	2001 Jan	11134245
Alteration of humoral and peripheral vascular responses during graded exercise in heart failure.	2001 Jan	11133893
Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme.	2001 Jan	11125020
An extended hydrophobic interactive surface of Yersinia pestis Caf1M chaperone is essential for subunit binding and F1 capsule assembly.	2001 Jan	11123684
Altered TNF-alpha, glucose, insulin, and amino acids in islets of Langerhans cultured in a microgravity model system.	2001 Jan	11120663
Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells.	2001 Jan	11120661
In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells.	2001 Jan	11115535
Lower serum activity of prolyl endopeptidase in anorexia and bulimia nervosa.	2001 Jan	11070331
Tec kinase signaling in T cells is regulated by phosphatidylinositol 3-kinase and the Tec pleckstrin homology domain.	2001 Jan 1	11123316
Substitution of Asp114 or Arg116 in the fingers domain of moloney murine leukemia virus reverse transcriptase affects interactions with the template-primer resulting in decreased processivity.	2001 Jan 12	11124910
Amino acid residues in ribonuclease MC1 from bitter gourd seeds which are essential for uridine specificity.	2001 Jan 16	11148047
Structure and organization of bacteriophage Pf3 probed by Raman and ultraviolet resonance Raman spectroscopy.	2001 Jan 16	11148039
Exercise training in coronary artery disease and coronary vasomotion.	2001 Jan 2	11136704
Strengthened arm-dimerization domain interactions in AraC.	2001 Jan 26	11069917
Mutations that affect ligand binding to the Escherichia coli aspartate receptor: implications for transmembrane signaling.	2001 Jan 26	11042221
Pharmacological profile of T-1032, a novel specific phosphodiesterase type 5 inhibitor, in isolated rat aorta and rabbit corpus cavernosum.	2001 Jan 5	11137871
Membrane binding motif of the P-type cardiotoxin.	2001 Jan 5	11114253
Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis.	2001 Jan 5	11114250
C60-Fullerene monomalonate adducts selectively inactivate neuronal nitric oxide synthase by uncoupling the formation of reactive oxygen intermediates from nitric oxide production.	2001 Jan 9	11141054
A single histidine residue determines the pH sensitivity of the pacemaker channel HCN2.	2001 Mar 2	11096117
Scanning mutagenesis reveals roles for helix n of the bacteriophage T7 RNA polymerase thumb subdomain in transcription complex stability, pausing, and termination.	2001 Mar 30	11124963
Substrate-binding clusters of the K+-transporting Kdp ATPase of Escherichia coli investigated by amber suppression scanning mutagenesis.	2001 Mar 30	11106663
Peptide leucine arginine, a potent immunomodulatory peptide isolated and structurally characterized from the skin of the Northern Leopard frog, Rana pipiens.	2001 Mar 30	11099505
Identification of the collagen-binding site of the von Willebrand factor A3-domain.	2001 Mar 30	11098050
The modulation of oxygen radical production by nitric oxide in mitochondria.	2001 Mar 9	11106647
Sequence requirements for the N-methyl-D-aspartate receptor antagonist activity of conantokin-R.	2001 Mar 9	11096077
The basis of prostaglandin synthesis in coral: molecular cloning and expression of a cyclooxygenase from the Arctic soft coral Gersemia fruticosa.	2001 Mar 9	11085996
Identification of the bile acid-binding site of the ileal lipid-binding protein by photoaffinity labeling, matrix-assisted laser desorption ionization-mass spectrometry, and NMR structure.	2001 Mar 9	11069906
Rare somatic p53 mutation identified in breast cancer: a case report.	2001 Mar-Apr	11125276
The role of nitric oxide on the relaxations of rabbit corpus cavernosum induced by Androctonus australis and Buthotus judaicus scorpion venoms.	2001 May	11072041

Patents

Sample Use Guides

In Vivo Use Guide

L-arginine has been studied at oral doses of 6 to 30 g/day for a variety of conditions. Many formulations have been used.

Route of Administration: Oral

In Vitro Use Guide

A strong inward current in X. laevis oocytes expressing 5.24 (C terminus of the homologous goldfish 5.24 receptor) when L-Arg (L-arginine) was applied at 10 uM. When testing chimera h6A/5.24 (h6A/5.24, containing the ligand binding amino-terminal domain (ATD) of hGPRC6A with the signal transducing transmembrane and C terminus of the homologous goldfish 5.24 receptor) in this system, the responses were obtained with L-Arg at 100 uM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:44:55 GMT 2023` Edited by `admin` on `Fri Dec 15 16:44:55 GMT 2023`
Record UNII	1221OL1Q9F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ARGININE CITRATE

Common Name

English

L-ARGININE, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (3:1)

Common Name

English

Arginine citrate [WHO-DD]

Common Name

English

Code System Code Type Description

PUBCHEM

71587350