Identification
- Summary
Phosphocreatine is a cardioprotective agent indicated for use in cardiac surgery.
- Generic Name
- Phosphocreatine
- DrugBank Accession Number
- DB13191
- Background
Phosphocreatine - or creatine phosphate - is the phosphorylated form of creatine. It is primarily found endogenously in the skeletal muscles of vertebrates where it serves a critical role as a rapidly acting energy buffer for muscle cell actions like contractions via its ability to regenerate adenosine triphosphate (ATP) from adenosine diphosphate (ADP).
- Type
- Small Molecule
- Groups
- Nutraceutical
- Structure
Structure for Phosphocreatine (DB13191)
- Weight
- Average: 211.1131
Monoisotopic: 211.035806957 - Chemical Formula
- C4H10N3O5P
- Synonyms
- Creatine phosphate
- Creatine phosphic acid
- Creatine-P
- Fosfocreatine
- N-(N-phosphonoamido)sarcosine
- N-(Phosphonoamidino)sarcosine
- N-phosphocreatine
- N-Phosphorylcreatine
- phosphorylcreatine
Pharmacology
- Indication
Phosphocreatine is a naturally occuring substance that is found predominantly in the skeletal muscles of vertebrates. Its primary utility within the body is to serve in the maintanence and recycling of adenosine triphosphate (ATP) for muscular activity like contractions.
Given this utility of phosphocreatine to recycle ATP, the most plausible therapeutic potentials for its use involve conditions caused by energy shortage or by increased energy requirements - such as in ischemic stroke and other cerebrovascular diseases. It is important to note however that relatively little clinical research has been done to significantly further the evidence for any such indications, although it is administered intravenously for cardiovascular conditions in some countries.
Additionally, because phosphocreatine is not regulated as a controlled substance it is taken as a supplement by some professional athletes as a means to perhaps increase short bursts of muscle strength or energy for professional athletics.
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- Contraindications & Blackbox Warnings
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Creatine is a naturally occurring chemical within the body and is primarily stored in skeletal muscle in both free and phosphorylated forms. Phosphocreatine is the name given to the phosphorylated form of creatine. Additionally, phosphocreatine can also be found in other areas of the body like the kidneys, liver, and brain. In fact, most in vivo synthesis of creatine occurs in the liver where amidine groups from arginine are transfered to glycine with the help of the glycine transaminidase enzyme to form guanidinoacetic acid. This acid is then methylated with the methyl group of S-adenosylmethionine via guanidinoacetate methyltransferase to generate creatine. The synthesized creatine is transported to storage sites in skeletal muscle via the bloodstream.
The phosphorylation of creatine is reversible in both a forwards and backwards reaction. That is, while phosphocreatine is capable of anaerobically donating a phosphate group to adenosine diphosphate (ADP) to regenerate ATP, at the same time excess ATP can be dephosphorylated during periods of low muscle activity to convert creatine to phosphocreatine. This dual activity in synthesizing phosphocreatine from excess levels of ATP during rest and use of phosphocreatine to regenerate ATP during high activity demonstrates the crucial utility of phosphocreatine in acting as an energy buffer in body mucle cells.
Phosphocreatine's fast regeneration of ATP is considered a coupled reaction - in essence, the energy released from transferring a donating a phosphate group from phosphocreatine is used to regenerate ATP. Phosphocreatine consequently plays an essential role in body tissues that have high, fluctuating energy requirments like muscle and brain tissues.
- Mechanism of action
Adenosine triphosphate (ATP) is the primary source of chemical energy that body muscles use to perform contractions. During such contraction processes, ATP molecules are depleted as they undergo hydrolysis reactions and become adenosine diphosphate (ADP). To maintain homeostasis in muscle activity, the ATP supply of muscles must be regenerated regularly.
Phosphocreatine occurs naturally within the body and is capable of regenerating ATP by transferring a high-energy phosphate from itself to ADP, resulting in the formation of ATP and creatine. This kind of regeneration of ATP with phosphocreatine typically occurs within seconds of intense muscular or neuronal effort, acting as a quickly accessible reserve of high-energy phosphates for the recycling of ATP in body muscle tissues. ATP recycling from phosphocreatine is in fact known as the quickest form of ATP regeneration.
Target Actions Organism AGuanidinoacetate N-methyltransferase product ofHumans ASodium- and chloride-dependent creatine transporter 1 Not Available Humans ACreatine kinase M-type ligandHumans ACreatine kinase U-type, mitochondrial ligandHumans ACreatine kinase S-type, mitochondrial ligandHumans ACreatine kinase B-type ligandHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Phosphocreatine is eliminated renally.
The end result of creatine degredation is the product creatinine, which enters the bloodstream from its storage sites in body muscle. When creatinine enters the renal parenchyma it is filtered in the renal glomerulus to be excreted in the urine.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Phosphocreatine which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. Aclidinium Aclidinium may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. Acrivastine Acrivastine may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Phosphocreatine which could result in a higher serum level. 
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- Not Available
Products
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Ingredient UNII CAS InChI Key Phosphocreatine sodium 79577SJY6E 922-32-7 RNTXMYSPASRLFT-UHFFFAOYSA-L
Categories
- ATC Codes
- C01EB06 — Fosfocreatine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acids and derivatives
- Alternative Parents
- Organic phosphoric acids and derivatives / Guanidines / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aliphatic acyclic compound / Alpha-amino acid or derivatives / Carbonyl group / Carboxylic acid / Guanidine / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Organic nitrogen compound / Organic oxide / Organic oxygen compound
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- phosphagen, phosphoamino acid (CHEBI:17287)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 020IUV4N33
- CAS number
- 67-07-2
- InChI Key
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N
- InChI
- InChI=1S/C4H10N3O5P/c1-7(2-3(8)9)4(5)6-13(10,11)12/h2H2,1H3,(H,8,9)(H4,5,6,10,11,12)
- IUPAC Name
- 2-(N-methyl-N'-phosphonocarbamimidamido)acetic acid
- SMILES
- CN(CC(O)=O)C(=N)NP(O)(O)=O
References
- General References
- Balestrino M, Sarocchi M, Adriano E, Spallarossa P: Potential of creatine or phosphocreatine supplementation in cerebrovascular disease and in ischemic heart disease. Amino Acids. 2016 Aug;48(8):1955-67. doi: 10.1007/s00726-016-2173-8. Epub 2016 Jan 21. [Article]
- Strumia E, Pelliccia F, D'Ambrosio G: Creatine phosphate: pharmacological and clinical perspectives. Adv Ther. 2012 Feb;29(2):99-123. doi: 10.1007/s12325-011-0091-4. [Article]
- Guimaraes-Ferreira L: Role of the phosphocreatine system on energetic homeostasis in skeletal and cardiac muscles. Einstein (Sao Paulo). 2014 Jan-Mar;12(1):126-31. [Article]
- External Links
- Human Metabolome Database
- HMDB0001511
- KEGG Compound
- C02305
- PubChem Compound
- 9548602
- PubChem Substance
- 347829286
- ChemSpider
- 567
- ChEBI
- 17287
- ChEMBL
- CHEMBL1204644
- ZINC
- ZINC000003869774
- Wikipedia
- Phosphocreatine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Cardiac Surgical Procedures (D006348) / Implantation, Heart Valve Prosthesis 1 2 Recruiting Treatment Depression 1 2 Unknown Status Treatment Major Depressive Disorder (MDD) 1 Not Available Unknown Status Supportive Care Valvular Heart Disease 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Capsule Injection, powder, for solution Intramuscular Injection, powder, for solution Intramuscular 100 MG/ML Injection, powder, for solution Intramuscular 20 MG/ML Injection, powder, for solution Intravenous Powder, for solution Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 194-195 °C www,chemspider.com boiling point (°C) 449.1±47.0 °C at 760 mmHg www.chemspider.com water solubility 3.52 mg/mL ALOGPS - Predicted Properties
Property Value Source Water Solubility 3.52 mg/mL ALOGPS logP -2 ALOGPS logP -2.3 Chemaxon logS -1.8 ALOGPS pKa (Strongest Acidic) -1.1 Chemaxon pKa (Strongest Basic) 13.57 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 133.95 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 53.18 m3·mol-1 Chemaxon Polarizability 16.82 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Product of
- General Function
- Methyltransferase activity
- Specific Function
- Not Available
- Gene Name
- GAMT
- Uniprot ID
- Q14353
- Uniprot Name
- Guanidinoacetate N-methyltransferase
- Molecular Weight
- 26317.925 Da
References
- Guimaraes-Ferreira L: Role of the phosphocreatine system on energetic homeostasis in skeletal and cardiac muscles. Einstein (Sao Paulo). 2014 Jan-Mar;12(1):126-31. [Article]
- Almeida LS, Vilarinho L, Darmin PS, Rosenberg EH, Martinez-Munoz C, Jakobs C, Salomons GS: A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. Mol Genet Metab. 2007 May;91(1):1-6. Epub 2007 Mar 1. [Article]
- Kan HE, Meeuwissen E, van Asten JJ, Veltien A, Isbrandt D, Heerschap A: Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy. J Appl Physiol (1985). 2007 Jun;102(6):2121-7. Epub 2007 Mar 8. [Article]
- Wang L, Zhang Y, Shao M, Zhang H: Spatiotemporal expression of the creatine metabolism related genes agat, gamt and ct1 during zebrafish embryogenesis. Int J Dev Biol. 2007;51(3):247-53. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- General Function
- Neurotransmitter:sodium symporter activity
- Specific Function
- Required for the uptake of creatine in muscles and brain.
- Gene Name
- SLC6A8
- Uniprot ID
- P48029
- Uniprot Name
- Sodium- and chloride-dependent creatine transporter 1
- Molecular Weight
- 70522.17 Da
References
- Rosenberg EH, Munoz CM, Degrauw TJ, Jakobs Cn, Salomons GS: Overexpression of wild-type creatine transporter (SLC6A8) restores creatine uptake in primary SLC6A8-deficient fibroblasts. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):345-6. [Article]
- Lunardi G, Parodi A, Perasso L, Pohvozcheva AV, Scarrone S, Adriano E, Florio T, Gandolfo C, Cupello A, Burov SV, Balestrino M: The creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds. Neuroscience. 2006 Nov 3;142(4):991-7. Epub 2006 Sep 1. [Article]
- Derave W, Straumann N, Olek RA, Hespel P: Electrolysis stimulates creatine transport and transporter cell surface expression in incubated mouse skeletal muscle: potential role of ROS. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1250-7. Epub 2006 Jul 18. [Article]
- Campistol J, Arias-Dimas A, Poo P, Pineda M, Hoffman M, Vilaseca MA, Artuch R, Ribes A: [Cerebral creatine transporter deficiency: an infradiagnosed neurometabolic disease]. Rev Neurol. 2007 Mar 16-31;44(6):343-7. [Article]
- Wang L, Zhang Y, Shao M, Zhang H: Spatiotemporal expression of the creatine metabolism related genes agat, gamt and ct1 during zebrafish embryogenesis. Int J Dev Biol. 2007;51(3):247-53. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Creatine kinase activity
- Specific Function
- Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with l...
- Gene Name
- CKM
- Uniprot ID
- P06732
- Uniprot Name
- Creatine kinase M-type
- Molecular Weight
- 43100.91 Da
References
- Zeng L, Hu Q, Wang X, Mansoor A, Lee J, Feygin J, Zhang G, Suntharalingam P, Boozer S, Mhashilkar A, Panetta CJ, Swingen C, Deans R, From AH, Bache RJ, Verfaillie CM, Zhang J: Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Circulation. 2007 Apr 10;115(14):1866-75. Epub 2007 Mar 26. [Article]
- Zhou DQ, Hu Y, Liu G, Gong L, Xi Y, Wen L: Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week 5000-m training programme. Br J Sports Med. 2006 Dec;40(12):988-91. Epub 2006 Sep 25. [Article]
- Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Creatine kinase activity
- Specific Function
- Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with l...
- Gene Name
- CKMT1A
- Uniprot ID
- P12532
- Uniprot Name
- Creatine kinase U-type, mitochondrial
- Molecular Weight
- 47036.3 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- Slenzka K, Appel R, Kappel Th, Rahmann H: Influence of altered gravity on brain cellular energy and plasma membrane metabolism of developing lower aquatic vertebrates. Adv Space Res. 1996;17(6-7):125-8. [Article]
- Wyss M, Schlegel J, James P, Eppenberger HM, Wallimann T: Mitochondrial creatine kinase from chicken brain. Purification, biophysical characterization, and generation of heterodimeric and heterooctameric molecules with subunits of other creatine kinase isoenzymes. J Biol Chem. 1990 Sep 15;265(26):15900-8. [Article]
- Muhlebach SM, Wirz T, Brandle U, Perriard JC: Evolution of the creative kinases. The chicken acidic type mitochondrial creatine kinase gene as the first nonmammalian gene. J Biol Chem. 1996 May 17;271(20):11920-9. [Article]
- Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Creatine kinase activity
- Specific Function
- Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with l...
- Gene Name
- CKMT2
- Uniprot ID
- P17540
- Uniprot Name
- Creatine kinase S-type, mitochondrial
- Molecular Weight
- 47504.08 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- Koufen P, Ruck A, Brdiczka D, Wendt S, Wallimann T, Stark G: Free radical-induced inactivation of creatine kinase: influence on the octameric and dimeric states of the mitochondrial enzyme (Mib-CK). Biochem J. 1999 Dec 1;344 Pt 2:413-7. [Article]
- Wyss M, James P, Schlegel J, Wallimann T: Limited proteolysis of creatine kinase. Implications for three-dimensional structure and for conformational substrates. Biochemistry. 1993 Oct 12;32(40):10727-35. [Article]
- Stachowiak O, Dolder M, Wallimann T, Richter C: Mitochondrial creatine kinase is a prime target of peroxynitrite-induced modification and inactivation. J Biol Chem. 1998 Jul 3;273(27):16694-9. [Article]
- Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with l...
- Gene Name
- CKB
- Uniprot ID
- P12277
- Uniprot Name
- Creatine kinase B-type
- Molecular Weight
- 42643.95 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- Koufen P, Ruck A, Brdiczka D, Wendt S, Wallimann T, Stark G: Free radical-induced inactivation of creatine kinase: influence on the octameric and dimeric states of the mitochondrial enzyme (Mib-CK). Biochem J. 1999 Dec 1;344 Pt 2:413-7. [Article]
- Wyss M, James P, Schlegel J, Wallimann T: Limited proteolysis of creatine kinase. Implications for three-dimensional structure and for conformational substrates. Biochemistry. 1993 Oct 12;32(40):10727-35. [Article]
- Stachowiak O, Dolder M, Wallimann T, Richter C: Mitochondrial creatine kinase is a prime target of peroxynitrite-induced modification and inactivation. J Biol Chem. 1998 Jul 3;273(27):16694-9. [Article]
- Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40. [Article]
Drug created at June 22, 2017 15:18 / Updated at June 05, 2021 09:12