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Identification
Name L-Citrulline
Accession Number DB00155 (NUTR00021)
Type small molecule
Groups approved, nutraceutical
Description

Citrulline is an amino acid. It is made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by NOS family. Its name is derived from citrullus, the Latin word for watermelon, from which it was first isolated.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
2-Amino-5-uredovaleric acid
Citrulline
delta-Ureidonorvaline
N5-(Aminocarbonyl)ornithine
N5-Carbamoyl-L-ornithine
N5-carbamoylornithine
N5-carbamylornithine
Sitrulline
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
  • Non-Essential Amino Acids
CAS number 372-75-8
Weight Average: 175.1857
Monoisotopic: 175.095691297
Chemical Formula C6H13N3O3
InChI Key InChIKey=RHGKLRLOHDJJDR-BYPYZUCNSA-N
InChI
InChI=1S/C6H13N3O3/c7-4(5(10)11)2-1-3-9-6(8)12/h4H,1-3,7H2,(H,10,11)(H3,8,9,12)/t4-/m0/s1
Plain Text
IUPAC Name
(2S)-2-amino-5-(carbamoylamino)pentanoic acid
SMILES
N[C@@H](CCCNC(N)=O)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
  • Carboxylic Acids and Derivatives
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Ureas and Derivatives
  • Carboxylic Acids and Derivatives
  • Carbamates and Derivatives
Pharmacology
Indication Used for nutritional supplementation, also for treating dietary shortage or imbalance.
Pharmacodynamics A non-essential amino acid and a precursor of arginine. Citrulline supplements have been claimed to promote energy levels, stimulate the immune system and help detoxify ammonia (a cell toxin). L-citrulline is made from L-ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from L-arginine as a by-product of the reaction catalyzed by the enzyme NO synthase. L-citrulline, while being an amino acid, is not involved in protein synthesis and is not one of the amino acids coded for by DNA. Although citrulline cannot be incorporated in proteins during protein synthesis, several proteins are known to contain citrulline as an amino acid. These citrulline residues are generated by a family of enzymes called peptidylarginine deiminases (PADs), which convert the amino acid arginine into citrulline. Proteins that contain citrulline residues include myelin basic protein (MBP), fillagrin and several histone proteins.
Mechanism of action L-citrulline is converted to L-arginine by argininosuccinate synthase. L-arginine is in turn responsible for citrulline's therapeutic affects. Many of L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3',5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase.

NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium.

All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, L-arginine could enhance endothelial-dependent vasodilation and NO production.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
L-citrulline powder 1.01 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 235.5 °C PhysProp
water solubility 200 g/L (at 20 °C) Not Available
logP -3.19 SANGSTER (1994)
pKa 2.43 (at 25 °C) KORTUM,G ET AL (1961)
Predicted Properties
Property Value Source
water solubility 2.18e+01 g/l ALOGPS
logP -3.3 ALOGPS
logP -3.9 ChemAxon
logS -0.9 ALOGPS
pKa (strongest acidic) 2.27 ChemAxon
pKa (strongest basic) 9.23 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 118.44 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 41.33 ChemAxon
polarizability 17.35 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C00327 Link_out
PubChem Compound 9750 Link_out
PubChem Substance 46506583 Link_out
ChemSpider 9367 Link_out
ChEBI 16349 Link_out
ChEMBL 16349 Link_out
PharmGKB PA164747225 Link_out
IUPHAR 722 Link_out
Guide to Pharmacology 722 Link_out
HET CIR Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (72.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Argininosuccinate synthase

Pharmacological action: unknown
Organism class: human
UniProt ID: P00966 Link_out
Gene: ASS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Braissant O, Honegger P, Loup M, Iwase K, Takiguchi M, Bachmann C: Hyperammonemia: regulation of argininosuccinate synthetase and argininosuccinate lyase genes in aggregating cell cultures of fetal rat brain. Neurosci Lett. 1999 May 7;266(2):89-92. Pubmed
  2. Braissant O, Gotoh T, Loup M, Mori M, Bachmann C: L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study. Brain Res Mol Brain Res. 1999 Jul 5;70(2):231-41. Pubmed
  3. Keilhoff G, Reiser M, Stanarius A, Aoki E, Wolf G: Citrulline immunohistochemistry for demonstration of NOS activity in vivo and in vitro. Nitric Oxide. 2000 Aug;4(4):343-53. Pubmed
  4. Zhang B, Cao GL, Domachowske J, Jackson MJ, Porasuphatana S, Rosen GM: Stable expression of varied levels of inducible nitric oxide synthase in primary cultures of endothelial cells. Anal Biochem. 2000 Nov 15;286(2):198-205. Pubmed
  5. Zhang WY, Gotoh T, Oyadomari S, Mori M: Coinduction of inducible nitric oxide synthase and arginine recycling enzymes in cytokine-stimulated PC12 cells and high output production of nitric oxide. Brain Res Mol Brain Res. 2000 Nov 10;83(1-2):1-8. Pubmed

2. NG,NG-dimethylarginine dimethylaminohydrolase 2

Pharmacological action: unknown

Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in nitric oxide generation

Organism class: human
UniProt ID: O95865 Link_out
Gene: DDAH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tran CT, Fox MF, Vallance P, Leiper JM: Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics. 2000 Aug 15;68(1):101-5. Pubmed
  2. Tain YL, Baylis C: Determination of dimethylarginine dimethylaminohydrolase activity in the kidney. Kidney Int. 2007 Oct;72(7):886-9. Epub 2007 Jul 25. Pubmed

3. Argininosuccinate synthase

Pharmacological action: unknown
Organism class: human
UniProt ID: Q5T6L4 Link_out
Gene: ASS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Husson A, Brasse-Lagnel C, Fairand A, Renouf S, Lavoinne A: Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle. Eur J Biochem. 2003 May;270(9):1887-99. Pubmed
  2. Hammermann R, Bliesener N, Mossner J, Klasen S, Wiesinger H, Wessler I, Racke K: Inability of rat alveolar macrophages to recycle L-citrulline to L-arginine despite induction of argininosuccinate synthetase mRNA and protein, and inhibition of nitric oxide synthesis by exogenous L-citrulline. Naunyn Schmiedebergs Arch Pharmacol. 1998 Dec;358(6):601-7. Pubmed
  3. Van Geldre LA, Timmermans JP, Lefebvre RA: L-citrulline recycling by argininosuccinate synthetase and lyase in rat gastric fundus. Eur J Pharmacol. 2002 Nov 29;455(2-3):149-60. Pubmed
  4. Zandvliet MM, Rothuizen J: Transient hyperammonemia due to urea cycle enzyme deficiency in Irish wolfhounds. J Vet Intern Med. 2007 Mar-Apr;21(2):215-8. Pubmed
  5. Takahashi H, Kagawa T, Kobayashi K, Hirabayashi H, Yui M, Begum L, Mine T, Takagi S, Saheki T, Shinohara Y: A case of adult-onset type II citrullinemia—deterioration of clinical course after infusion of hyperosmotic and high sugar solutions. Med Sci Monit. 2006 Feb;12(2):CS13-5. Epub 2006 Jan 26. Pubmed

4. NG,NG-dimethylarginine dimethylaminohydrolase 1

Pharmacological action: unknown

Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in nitric oxide generation

Organism class: human
UniProt ID: O94760 Link_out
Gene: DDAH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mishima T, Hamada T, Ui-Tei K, Takahashi F, Miyata Y, Imaki J, Suzuki H, Yamashita K: Expression of DDAH1 in chick and rat embryos. Brain Res Dev Brain Res. 2004 Feb 20;148(2):223-32. Pubmed
  2. Tran CT, Fox MF, Vallance P, Leiper JM: Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics. 2000 Aug 15;68(1):101-5. Pubmed
  3. Arrigoni FI, Vallance P, Haworth SG, Leiper JM: Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation. 2003 Mar 4;107(8):1195-201. Pubmed

5. Ornithine carbamoyltransferase, mitochondrial

Pharmacological action: unknown
Organism class: human
UniProt ID: P00480 Link_out
Gene: OTC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Quintero MJ, Muro-Pastor AM, Herrero A, Flores E: Arginine catabolism in the cyanobacterium Synechocystis sp. Strain PCC 6803 involves the urea cycle and arginase pathway. J Bacteriol. 2000 Feb;182(4):1008-15. Pubmed
  2. Morizono H, Cabrera-Luque J, Shi D, Gallegos R, Yamaguchi S, Yu X, Allewell NM, Malamy MH, Tuchman M: Acetylornithine transcarbamylase: a novel enzyme in arginine biosynthesis. J Bacteriol. 2006 Apr;188(8):2974-82. Pubmed

6. Nitric-oxide synthase, brain

Pharmacological action: unknown

Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter

Organism class: human
UniProt ID: P29475 Link_out
Gene: NOS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kominami S, Yamazaki T, Koga T, Hori H: EPR studies on the photo-induced intermediates of ferric NO complexes of rat neuronal nitric oxide synthase trapped at low temperature. J Biochem (Tokyo). 1999 Oct;126(4):756-61. Pubmed
  2. Giraldi-Guimaraes A, Tenorio F, Bruning G, Mayer B, Mendez-Otero R, Cavalcante LA: Nitric oxide synthase expression in the opossum superior colliculus: a histochemical, immunohistochemical and biochemical study. Brain Behav Evol. 1999 Dec;54(6):303-13. Pubmed
  3. Perry JM, Zhao Y, Marletta MA: Cu2+ and Zn2+ inhibit nitric-oxide synthase through an interaction with the reductase domain. J Biol Chem. 2000 May 12;275(19):14070-6. Pubmed
  4. Adak S, Wang Q, Stuehr DJ: Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric-oxide synthase. Implications for mechanism. J Biol Chem. 2000 Oct 27;275(43):33554-61. Pubmed
  5. Yu W, Juang S, Lee J, Liu T, Cheng J: Decrease of neuronal nitric oxide synthase in the cerebellum of aged rats. Neurosci Lett. 2000 Sep 8;291(1):37-40. Pubmed

7. Nitric oxide synthase, inducible

Pharmacological action: unknown

Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions

Organism class: human
UniProt ID: P35228 Link_out
Gene: NOS2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cunningham JM, Rayne RC: Radiochemical measurement of NOS activity by conversion of [14C]L-arginine to citrulline using HPLC separation. Methods Mol Biol. 1998;100:75-81. Pubmed
  2. Keilhoff G, Reiser M, Stanarius A, Aoki E, Wolf G: Citrulline immunohistochemistry for demonstration of NOS activity in vivo and in vitro. Nitric Oxide. 2000 Aug;4(4):343-53. Pubmed
  3. Conrad KP, Powers RW, Davis AK, Novak J: Citrulline is not the major product using the standard “NOS activity” assay on renal cortical homogenates. Am J Physiol Regul Integr Comp Physiol. 2002 Jan;282(1):R303-10. Pubmed
  4. Knowles RG, Salter M: Measurement of NOS activity by conversion of radiolabeled arginine to citrulline using ion-exchange separation. Methods Mol Biol. 1998;100:67-73. Pubmed
  5. Yi GB, McClendon D, Desaiah D, Goddard J, Lister A, Moffitt J, Meer RK, deShazo R, Lee KS, Rockhold RW: Fire ant venom alkaloid, isosolenopsin A, a potent and selective inhibitor of neuronal nitric oxide synthase. Int J Toxicol. 2003 Mar-Apr;22(2):81-6. Pubmed

8. Nitric-oxide synthase, endothelial

Pharmacological action: unknown

Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. No mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets

Organism class: human
UniProt ID: P29474 Link_out
Gene: NOS3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hayakawa H, Raij L: Relationship between hypercholesterolaemia, endothelial dysfunction and hypertension. J Hypertens. 1999 May;17(5):611-9. Pubmed
  2. Trovati M, Massucco P, Mattiello L, Costamagna C, Aldieri E, Cavalot F, Anfossi G, Bosia A, Ghigo D: Human vascular smooth muscle cells express a constitutive nitric oxide synthase that insulin rapidly activates, thus increasing guanosine 3’:5’-cyclic monophosphate and adenosine 3’:5’-cyclic monophosphate concentrations. Diabetologia. 1999 Jul;42(7):831-9. Pubmed
  3. McDuffie JE, Coaxum SD, Maleque MA: 5-hydroxytryptamine evokes endothelial nitric oxide synthase activation in bovine aortic endothelial cell cultures. Proc Soc Exp Biol Med. 1999 Sep;221(4):386-90. Pubmed
  4. Tan E, Gurjar MV, Sharma RV, Bhalla RC: Estrogen receptor-alpha gene transfer into bovine aortic endothelial cells induces eNOS gene expression and inhibits cell migration. Cardiovasc Res. 1999 Aug 15;43(3):788-97. Pubmed
  5. Abu-Soud HM, Ichimori K, Presta A, Stuehr DJ: Electron transfer, oxygen binding, and nitric oxide feedback inhibition in endothelial nitric-oxide synthase. J Biol Chem. 2000 Jun 9;275(23):17349-57. Pubmed

9. Protein-arginine deiminase type-6

Pharmacological action: unknown

Catalyzes the deimination of arginine residues of proteins. May be involved in cytoskeletal reorganization in the egg and early embryo

Organism class: human
UniProt ID: Q6TGC4 Link_out
Gene: PADI6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

10. Protein-arginine deiminase type-1

Pharmacological action: unknown

Catalyzes the deimination of arginine residues of proteins

Organism class: human
UniProt ID: Q9ULC6 Link_out
Gene: PADI1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Iida A, Nakamura Y: Identification of 45 novel SNPs in the 83-kb region containing peptidylarginine deiminase types 1 and 3 loci on chromosomal band 1p36.13. J Hum Genet. 2004;49(7):387-90. Epub 2004 May 19. Pubmed

11. Protein-arginine deiminase type-3

Pharmacological action: unknown

Catalyzes the deimination of arginine residues of proteins

Organism class: human
UniProt ID: Q9ULW8 Link_out
Gene: PADI3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dong S, Kanno T, Yamaki A, Kojima T, Shiraiwa M, Kawada A, Mechin MC, Chavanas S, Serre G, Simon M, Takahara H: NF-Y and Sp1/Sp3 are involved in the transcriptional regulation of the peptidylarginine deiminase type III gene (PADI3) in human keratinocytes. Biochem J. 2006 Aug 1;397(3):449-59. Pubmed
  2. Iida A, Nakamura Y: Identification of 45 novel SNPs in the 83-kb region containing peptidylarginine deiminase types 1 and 3 loci on chromosomal band 1p36.13. J Hum Genet. 2004;49(7):387-90. Epub 2004 May 19. Pubmed
  3. Kanno T, Kawada A, Yamanouchi J, Yosida-Noro C, Yoshiki A, Shiraiwa M, Kusakabe M, Manabe M, Tezuka T, Takahara H: Human peptidylarginine deiminase type III: molecular cloning and nucleotide sequence of the cDNA, properties of the recombinant enzyme, and immunohistochemical localization in human skin. J Invest Dermatol. 2000 Nov;115(5):813-23. Pubmed

12. Protein-arginine deiminase type-2

Pharmacological action: unknown

Catalyzes the deimination of arginine residues of proteins

Organism class: human
UniProt ID: Q9Y2J8 Link_out
Gene: PADI2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dong S, Kojima T, Shiraiwa M, Mechin MC, Chavanas S, Serre G, Simon M, Kawada A, Takahara H: Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors. J Invest Dermatol. 2005 May;124(5):1026-33. Pubmed

13. Protein-arginine deiminase type-4

Pharmacological action: unknown

Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1

Organism class: human
UniProt ID: Q9UM07 Link_out
Gene: PADI4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y, Roeder RG, Clarke S, Stallcup MR, Allis CD, Coonrod SA: Human PAD4 regulates histone arginine methylation levels via demethylimination. Science. 2004 Oct 8;306(5694):279-83. Epub 2004 Sep 2. Pubmed
  2. Wysocka J, Allis CD, Coonrod S: Histone arginine methylation and its dynamic regulation. Front Biosci. 2006 Jan 1;11:344-55. Pubmed
  3. Yamamoto K, Yamada R: Genome-wide single nucleotide polymorphism analyses of rheumatoid arthritis. J Autoimmun. 2005;25 Suppl:12-5. Epub 2005 Nov 2. Pubmed
  4. Chang X, Han J: Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors. Mol Carcinog. 2006 Mar;45(3):183-96. Pubmed
  5. Okazaki Y, Suzuki A, Sawada T, Ohtake-Yamanaka M, Inoue T, Hasebe T, Yamada R, Yamamoto K: Identification of citrullinated eukaryotic translation initiation factor 4G1 as novel autoantigen in rheumatoid arthritis. Biochem Biophys Res Commun. 2006 Mar 3;341(1):94-100. Epub 2006 Jan 6. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19