ARGININE GLUTAMATE

First approved in 1957

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C6H14N4O2.C5H9NO4
Molecular Weight	321.3302
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=RVEWUBJVAHOGKA-WOYAITHZSA-N

InChI=1S/C6H14N4O2.C5H9NO4/c7-4(5(11)12)2-1-3-10-6(8)9;6-3(5(9)10)1-2-4(7)8/h4H,1-3,7H2,(H,11,12)(H4,8,9,10);3H,1-2,6H2,(H,7,8)(H,9,10)/t4-;3-/m00/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	C5H9NO4
Molecular Weight	147.1293
Charge	0
Count

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

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
Renal response during acute unilateral ureteral obstruction in rats.	2001	11135389
AGE in micro- and macroangiopathy.	2001	11125555
Internal ribosome entry site-mediated translation of a mammalian mRNA is regulated by amino acid availability.	2001 Apr 13	11114306
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
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
A positively charged cluster formed in the heme-distal pocket of cytochrome P450nor is essential for interaction with NADH.	2001 Feb 16	11076941
Kinetics of CO and NO ligation with the Cys(331)-->Ala mutant of neuronal nitric-oxide synthase.	2001 Feb 16	11067850
Increased affinity of c-Myb for CREB-binding protein (CBP) after CBP-induced acetylation.	2001 Feb 2	11073948
Amino acid residues outside of the pore region contribute to N-type calcium channel permeation.	2001 Feb 23	11120735
Early glycation products produce pentosidine cross-links on native proteins. novel mechanism of pentosidine formation and propagation of glycation.	2001 Feb 9	11076948
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
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
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
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
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
Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells.	2001 Jan	11120661
Buffering action of endogenous nitric oxide on the adrenocortical secretagogue effect of endothelins in the rat.	2001 Jan	11115609
In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells.	2001 Jan	11115535
The common Arg972 polymorphism in insulin receptor substrate-1 causes apoptosis of human pancreatic islets.	2001 Jan	11099486
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
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
Strengthened arm-dimerization domain interactions in AraC.	2001 Jan 26	11069917
The role of nitric oxide in bradycardia of rats with obstructive cholestasis.	2001 Jan 5	11137868
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
Acetaldehyde, a metabolite of ethanol, activates the hypothalamic-pituitary-adrenal axis in the rat.	2001 Jan-Feb	11139417
Translocation of jellyfish green fluorescent protein via the Tat system of Escherichia coli and change of its periplasmic localization in response to osmotic up-shock.	2001 Mar 16	11099493
Identification and analysis of the acyl carrier protein (ACP) docking site on beta-ketoacyl-ACP synthase III.	2001 Mar 16	11078736
Phage display-selected sequences of the heavy-chain CDR3 loop of the anti-digoxin antibody 26-10 define a high affinity binding site for position 16-substituted analogs of digoxin.	2001 Mar 16	11060305
A single histidine residue determines the pH sensitivity of the pacemaker channel HCN2.	2001 Mar 2	11096117
The molecular mechanism for the genetic disorder familial defective apolipoprotein B100.	2001 Mar 23	11115503
Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages.	2001 Mar 30	11136724
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
The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine.	2001 Mar 9	11096119
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
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 14:58:31 GMT 2023` Edited by `admin` on `Fri Dec 15 14:58:31 GMT 2023`
Record UNII	TU1X77K34Q
Record Status	`Validated (UNII)`
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Name

Type

Language

ARGININE GLUTAMATE

Official Name

English

ARGININE GLUTAMATE [INCI]

Common Name

English

ARGININE GLUTAMATE [MI]

Common Name

English

ARGININE GLUTAMATE [MART.]

Common Name

English

L-ARGININE L-GLUTAMATE HYDRATE [JAN]

Common Name

English

MODUMATE

Brand Name

English

ARGININE GLUTAMATE [USAN]

Common Name

English

L-ARGININE L-GLUTAMATE (1:1)

Common Name

English

Arginine glutamate [WHO-DD]

Common Name

English

NSC-122009

Code

English

Classification Tree Code System Code

WHO-ATC

A05BA01