ARGININE BUTYRATE

First approved in 1957

Details

Stereochemistry	ABSOLUTE
Molecular Formula	3C6H14N4O2.4C4H8O2
Molecular Weight	875.0234
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC(O)=O.CCCC(O)=O.CCCC(O)=O.CCCC(O)=O.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

InChI

InChIKey=ZVEMACCDKBQNGX-KALODSIISA-N

InChI=1S/3C6H14N4O2.4C4H8O2/c3*7-4(5(11)12)2-1-3-10-6(8)9;4*1-2-3-4(5)6/h3*4H,1-3,7H2,(H,11,12)(H4,8,9,10);4*2-3H2,1H3,(H,5,6)/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	C4H8O2
Molecular Weight	88.1051
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
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
Novel mutations in the GALK1 gene in patients with galactokinase deficiency.	2001	11139256
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
Renal response during acute unilateral ureteral obstruction in rats.	2001	11135389
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
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
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
Biglycan, a vascular proteoglycan, binds differently to HDL2 and HDL3: role of apoE.	2001 Jan	11145944
Fibroblast growth factor-2 stimulates endothelial nitric oxide synthase expression and inhibits apoptosis by a nitric oxide-dependent pathway in Nb2 lymphoma cells.	2001 Jan	11145569
Differential effects of glucagon-like peptide-1 (7-36)amide versus cholecystokinin on arginine-induced islet hormone release in vivo and in vitro.	2001 Jan	11138972
Effect of AVT antisense oligodeoxynucleotides on AVT release induced by hypertonic stimulation in chicks.	2001 Jan	11137447
Impaired renal vascular endothelial function in vitro in experimental hypercholesterolemia.	2001 Jan	11137100
How the Pseudomonas aeruginosa ExoS toxin downregulates Rac.	2001 Jan	11135665
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
[Ca(2+)](i) signaling in renal arterial smooth muscle cells of pregnant rat is enhanced during inhibition of NOS.	2001 Jan	11124138
An extended hydrophobic interactive surface of Yersinia pestis Caf1M chaperone is essential for subunit binding and F1 capsule assembly.	2001 Jan	11123684
Increased colocalization of corticotropin-releasing factor and arginine vasopressin in paraventricular neurones of the hypothalamus in lactating rats: evidence from immunotargeted lesions and immunohistochemistry.	2001 Jan	11123517
A metabolic fragment of bradykinin, Arg-Pro-Pro-Gly-Phe, protects against the deleterious effects of lipopolysaccharide in rats.	2001 Jan	11123364
Altered endothelium-dependent relaxations in lambs with high pulmonary blood flow and pulmonary hypertension.	2001 Jan	11123246
Relationship between flow rate and NO production in postnatal mesenteric arteries.	2001 Jan	11123196
Altered TNF-alpha, glucose, insulin, and amino acids in islets of Langerhans cultured in a microgravity model system.	2001 Jan	11120663
Distinct T cell developmental consequences in humans and mice expressing identical mutations in the DLAARN motif of ZAP-70.	2001 Jan 1	11123350
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
Glutamine metabolism to glucosamine is necessary for glutamine inhibition of endothelial nitric oxide synthesis.	2001 Jan 15	11139387
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
Insights into the molecular basis for the carbenicillinase activity of PSE-4 beta-lactamase from crystallographic and kinetic studies.	2001 Jan 16	11148033
Strain is more important than electrostatic interaction in controlling the pKa of the catalytic group in aspartate aminotransferase.	2001 Jan 16	11148029
Upregulation of the nitric oxide-cGMP pathway in aged myocardium: physiological response to l-arginine.	2001 Jan 19	11139480
Exercise training in coronary artery disease and coronary vasomotion.	2001 Jan 2	11136704
Site-specific single amino acid changes to Lys or Arg in the central region of the movement protein of a hybrid bromovirus are required for adaptation to a nonhost.	2001 Jan 5	11145888
Pharmacological profile of T-1032, a novel specific phosphodiesterase type 5 inhibitor, in isolated rat aorta and rabbit corpus cavernosum.	2001 Jan 5	11137871
The role of nitric oxide in bradycardia of rats with obstructive cholestasis.	2001 Jan 5	11137868
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
Acetaldehyde, a metabolite of ethanol, activates the hypothalamic-pituitary-adrenal axis in the rat.	2001 Jan-Feb	11139417
Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages.	2001 Mar 30	11136724
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
Rare somatic p53 mutation identified in breast cancer: a case report.	2001 Mar-Apr	11125276

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 15:48:49 GMT 2023` Edited by `admin` on `Fri Dec 15 15:48:49 GMT 2023`
Record UNII	IK8S1P79MU
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ARGININE BUTYRATE

Common Name

English

VX-105

Common Name

English

HQK-1004

Code

English

L-ARGININE, BUTANOATE (3:4)

Common Name

English

Arginine butanoate [WHO-DD]

Common Name

English

VX 105

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

82094