2-(carbamimidoyl-methyl-amino) ethoxyphosphonic acid

2-(Carbamimidoyl-methyl-amino)ethoxyphosphonic Acid (Creatinol-O-Phosphate): A Comprehensive Reference

1. Identity and Chemical Characterization

Nomenclature and Synonyms

2-(Carbamimidoyl-methyl-amino)ethoxyphosphonic acid is the systematic chemical name for the compound more widely recognized in the scientific and pharmaceutical literature as creatinol-O-phosphate (COP), also spelled creatinolfosfate (Italian and Spanish orthography) and creatinol phosphate. It is a cardioprotective drug and structural analog of creatine, not to be confused with phosphocreatine, which is a phosphorylated creatine molecule. Additional synonyms documented in reference databases include:

• N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate — the systematic pharmacological name used in most clinical and toxicological publications from the 1970s and 1980s.
• Aplodan — the originating Italian trade name under which it was marketed by Simes (Milan, Italy) and used in European cardiology.
• Creatinolfosfate — registered in the Index Nominum International Drug Discovery, published by the Swiss Pharmaceutical Society.

The compound is listed in the NIH National Center for Advancing Translational Sciences (NCATS) Inxight Drugs database as CREATINOLFOSFATE, with the notation that it is possibly marketed outside the US, its originating source being Aplodan by Simes, Italy.

Creatinol-O-phosphate carries the Chemical Abstracts Service (CAS) registry number 6903-79-3. Its molecular weight is 197.13 g/mol, and it likely exists in a zwitterionic form to some extent.

Molecular Structure

COP is structurally related to creatine but distinct from it. Whereas creatine (N-methyl-N-guanidinoacetic acid, CAS 57-00-1) carries a carboxylic acid group at its terminal carbon, COP replaces that carboxylic acid with a phosphonate ester linked via an oxyethyl bridge, creating the IUPAC name 2-(carbamimidoyl-methyl-amino)ethoxyphosphonic acid. This structural distinction is critical: pharmacological research demonstrated that creatinol-O-phosphate is distinguished with respect to the class of beta-blocking agents and from that of calcium antagonists, recommended for similar therapeutic uses. It differs not only from a pharmacological point of view, but also because it does not produce side effects such as the negative inotropic action and the atrioventricular block.

The molecular formula is C₄H₁₂N₃O₄P. COP has an aqueous solubility of approximately 5 g/L at 20°C, which is inferior to several other creatine derivatives.

Origin: Synthetic, Not Botanical

COP has no botanical source. Creatinol O-phosphate (COP; Aplodan) is a synthetic drug first synthesized by Ferrari and Casagrande in 1965. It was not isolated from a plant or animal tissue but was purpose-designed as a creatine analog with cardioprotective properties. It is therefore properly classified as a synthetic small molecule with no traditional herbal or dietary use prior to its pharmaceutical development.

Common Preparations and Forms

The literature describes stable aqueous compositions of biologically active creatinol-O-phosphate species, with preparations described for oral use, for injection, and for topical administration. In the principal clinical tolerance study, COP was administered intravenously to volunteer human subjects; three dosage groups received 1,020 mg, 2,040 mg, and 3,060 mg respectively, compared with a placebo group. In its European pharmaceutical history, it was formulated primarily for parenteral (intravenous and intramuscular) use in hospital cardiology settings. In the single muscular performance clinical trial, fifty female patients were treated intramuscularly and intravenously with COP.

In the contemporary sports supplement market, COP has been formulated into oral capsule and powder blends. Products such as "Aplodan" (a dietary supplement distinct from the original pharmaceutical) contain 2-(carbamimidoyl-methyl-amino)ethoxyphosphonic acid as a primary component. The compound in that supplement product is also known as creatinol-O-phosphate (COP).

2. Historical and Medical Background

Development and European Medical Use

Developed in the mid-20th century, COP was initially used in Europe as a cardioprotective agent. Its primary historical use was as an adjunct therapy for patients suffering from cardiac insufficiency, arrhythmias, and other heart-related ailments. The compound's first reported synthesis was in 1965 (Ferrari and Casagrande), and its initial pharmacological characterization appears in the peer-reviewed literature from the late 1960s through the 1970s, concentrated primarily in Italian and Belgian research groups.

The compound was proposed for the prevention and therapy of myocardial infarction; in its free form or as a sodium salt, it was advanced for the treatment of cardiovascular diseases including coronary insufficiency and cor pulmonale (right heart failure).

A dedicated symposium supplement of the journal Arzneimittelforschung (Drug Research) was published in 1979 (volume 29, issue 9a), containing multiple original clinical and pharmacological investigations of COP, reflecting its status at that time as an emerging cardiovascular therapeutic agent in European medicine. The compound was listed in Martindale: The Complete Drug Reference, 32nd edition (London Pharmaceutical Press, 2002, p. 1601), and in the European Drug Index (European Society of Clinical Pharmacy, Stuttgart, 1997, p. 91), documenting its recognition within formal European pharmacological reference works.

There is no documented record of traditional use of this compound in any pre-modern medicine system anywhere in the world, nor is there any botanical tradition associated with it, as it is entirely synthetic in origin.

3. Key Constituents, Active Compounds, and Established Mechanisms of Action

The Compound Itself as Active Substance

COP is a single-molecule active substance rather than a multi-constituent extract. Its pharmacological and biochemical activity arises from the intact molecule and its metabolites. Two overarching mechanisms have been described in the peer-reviewed literature:

Mechanism 1: Creatine Precursor / Phosphate Donor Activity

Based on findings that intravenous administration of COP in healthy human subjects led to increased values of creatinine in urine, it is speculated that creatinol acts as a precursor of creatine and is metabolized into creatine within the body. The increased urinary values are derived from the degradation of creatine into creatinine through the typical biochemical pathways.

The detection of increased creatinine resulting from COP administration indicates that COP may serve as a source of physiological creatine, which provides well-established benefits to muscle metabolism and athletic performance mainly through the regeneration of phosphocreatine. COP contains within it both creatine and phosphate to necessitate the regeneration of phosphocreatine.

COP acts as a vehicle to transport phosphate into the cells, where it can then dissociate to form the high-energy molecule ATP or to phosphorylate creatine to phosphocreatine, which can then donate the phosphate to ADP to form ATP for use in muscular contractions.

Acting similarly to creatine phosphate in donating the phosphate group for converting ADP to ATP in muscles, COP has been proposed to supply energy to muscles effectively. However, it is important to note that this proposed superiority over creatine phosphate appears in patent literature rather than in independently published clinical comparisons.

Mechanism 2: Inhibition of Creatine Kinase (CK) Leakage

A distinct proposed mechanism, described in US Patent 7,375,097 (Aplodan Formulations Ltd.), relates to COP's effects on the enzyme creatine kinase (CK):

COP inhibits the leakage of the ATP-dependent enzyme creatine kinase. Via the inhibition of creatine kinase leakage, ATP is not utilized in the conversion of creatine to phosphocreatine, thereby making it available for use in muscular contractions. The increase in availability leads to longer endurance and more forceful muscular contractions.

COP has been shown to afford cardioprotection and has been shown to reduce the leakage of CK as well as several other enzymes in human patients suffering from acute myocardial infarction. The same patent cites published work from the 1979 Arzneimittelforschung symposium to support this claim.

Mechanism 3: Intracellular pH Buffering and Prolongation of Anaerobic Glycolysis

A third mechanism, cited in reference to Italian-language research, proposes that COP acts as an intracellular buffer against lactic acid accumulation during intense muscle activity. Once muscle cells are saturated, the primary action of creatinol-O-phosphate is to prolong anaerobic glycolysis in the presence of excess lactic acid. COP is said to override the mechanism of excess lactic acid accumulation by acting as an intracellular buffer, preventing a dramatic drop in pH and allowing muscle contractions to continue beyond the point at which the body would normally shut down activity.

This compound exerts its cardioprotective effect by action on anaerobic glycolysis.

Mechanism 4: Membrane Stabilization

In previous pharmacological and clinical research, COP showed useful effects on both normal and ischemic heart. These effects can be traced to a protective action of COP on the cell membrane. In animal studies of isolated heart tissue, COP demonstrated positive inotropic (contractility-enhancing) properties:

In normoxia, creatinol-O-phosphate (100 μmol/L) evoked a positive inotropic effect only when glucose was present. When COP was present during hypoxia, the recovery of contraction after reoxygenation was improved in a dose-dependent manner. When COP was present before ischemia, the recovery of contractility after reperfusion was higher than in controls; and the presence of COP during reperfusion after ischemia accelerated the recovery of contractility.

COP has a positive inotropic effect on the isolated rabbit atrium, and an ability to antagonize the toxic action of digitalis on the isolated atrium of rabbits previously treated with EDTA.

Hemodynamic and Metabolic Effects (Animal Data)

The effects of COP (Aplodan) have been studied on haemodynamics and cardiac metabolism of virtually normal heart (conscious dogs with electromagnetic probes chronically implanted) and progressively failing heart (open-chest anaesthetized dogs). COP in both series of experiments increased cardiac work and improved some myocardial metabolic parameters — including delta redox potential across the heart, lactate/pyruvate ratio, and excess lactate — probably by enhancing the myocardial oxygen supply-consumption ratio, and consequently increasing the amount of oxygen available for energetic reactions in the cardiac muscle and possibly in other tissues as well.

4. Scientific Evidence by Area of Application

4.1 Cardiovascular / Cardioprotective Applications

Evidence in Patients with Coronary Insufficiency (Human, Double-Blind)

The most rigorous human evidence for COP derives from a small number of double-blind clinical trials published in 1979, all concentrated in the dedicated Arzneimittelforschung supplement.

N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol-O-phosphate, COP) was tested in patients suffering from inadequate coronary circulation — 12 patients had a recent myocardial infarction and 13 were suffering from angina pectoris — versus a reference substance (solvent of COP) in a double-blind study. COP improved rhythm disturbances, chest pains, and symptoms of contractility failure to a statistically significant degree. The study was small, the comparator was not an active drug but the solvent vehicle, and the findings have not been replicated in larger randomized controlled trials.

Evidence in Ventricular Arrhythmia (Human, Double-Blind)

In a double-blind investigation, COP was tested versus the solvent of COP on volunteers affected by ischemic heart disease with persistent ventricular premature beats (VPB). COP was able to reduce VPB by 50–100% in 85% of the volunteers treated. This finding, together with the virtual absence of side-effects, led the authors to conclude that COP merits more extensive investigations in view of its clinical employment alone or in association with specific antiarrhythmic agents. Those more extensive investigations were never published in the accessible peer-reviewed literature.

Electrophysiological Effects (Human, Small Case Series)

The possible electrophysiological effects of COP were assessed in 6 patients, some of whom were free of excitation-conduction disturbances while others were suffering from sinoatrial automaticity or AV conduction alterations. When nodal AV conduction was slowed by iatrogenic or functional factors, COP as well as atropine improved it; thus both COP and atropine acted on the non-organic component of conduction disturbances. The organic component was not affected. The effect of atropine was more evident than that of COP. All other electrophysiological parameters were not affected by COP. This was an uncontrolled, six-patient pilot observation.

Effects on Serum Enzymes in Acute Myocardial Infarction

Research by Knippel et al. (published in Arzneimittelforschung 1979;29(9a):1480–2), cited in US Patent 7,375,097, examined COP's effects on serum enzyme levels in acute myocardial infarction patients. COP was shown to reduce the leakage of CK as well as several other enzymes in human patients suffering from acute myocardial infarction. The original paper is not freely accessible in English translation, and no subsequent large replication trial has been identified.

Animal Evidence: Isoprenaline-Induced Myocardial Lesions

Multiple in vivo animal studies examined COP's ability to attenuate experimentally induced myocardial damage. It was demonstrated that COP causes the number and the surface extension of ischemic lesions — induced by subcutaneous injection of isoprenaline in rats — to be reduced. Pre-treatment with COP significantly reduces heart damage and ionic imbalances induced by isoprenaline in rats.

Evidence Strength Assessment — Cardiovascular

The available human clinical evidence is limited in quality and volume: the trials are small, are decades old, were not replicated in larger randomized controlled trials, used vehicle-only (not active drug) comparators, and were conducted without modern methodological standards. Some cardiology research and animal studies suggest that COP supports myocardial energetics and protects against ischemic stress; however, clinical evidence in humans is limited and requires more robust trials. Animal and in vitro evidence is more extensive but cannot be directly extrapolated to human outcomes.

4.2 Skeletal Muscle Performance and Ergogenics

Hand Grip Strength (Human, Controlled Clinical Trial)

Only one study investigated the ability of COP to improve muscular performance. Fifty female patients were treated intramuscularly and intravenously with COP, and performance was tested using a Martin Vigorimeter to measure muscle strength in both hands. The administration of COP resulted in a statistically significant improvement in hand strength. Published by Nicaise J. in Current Therapeutic Research (1975;17(6):531–534), this study is the sole published controlled clinical trial addressing COP's ergogenic effects. It used parenteral rather than oral administration, enrolled a patient (not athletic) population, and measured a low-demand functional endpoint rather than athletic performance metrics.

In the patent, the manufacturer cites two older studies: one showing COP increased hand grip strength, the other showing "improved muscular performance" in "elderly subjects."

Evidence Strength Assessment — Muscular Performance

Scientific studies on COP are relatively limited, especially in the context of sports nutrition. Early clinical research focused on its use as an adjunct therapy for cardiac patients. There is a lack of clinical studies conducted with creatinol-O-phosphate that assess its benefits on exercise performance. Despite this, it is present in many supplements available today. No published randomized controlled trial has evaluated oral COP supplementation against placebo in a healthy, athletic population using validated performance endpoints.

4.3 Anti-Arrhythmic Effects

In preclinical models, COP demonstrated protective effects against experimentally induced cardiac arrhythmias. The activity of COP on two experimental arrhythmia models was investigated. The substance proved to be active in delaying the onset time of aconitine-induced arrhythmias in guinea-pig atria. COP also showed a definite antagonizing activity against chloroform-induced ventricular fibrillation in mice.

Aplodan (creatinol-O-phosphate) is classified as an antiischemic and antiarrhythmic agent with a protective action on the cell membrane. This classification reflects pharmacological and small-scale clinical evidence accumulated in the 1970s.

4.4 Relationship to the Creatine Kinase–Phosphocreatine Energy System

To contextualize COP's proposed mechanisms, it is useful to understand the creatine kinase system it targets. Creatine kinase catalyzes the reversible transfer of the N-phosphoryl group from phosphocreatine to ADP to regenerate ATP, and plays a key role in the energy homeostasis of cells with intermittently high, fluctuating energy requirements — such as skeletal and cardiac muscle, neurons, photoreceptors, spermatozoa, and electrocytes.

A large body of research indicates that the loss of cellular ATP due to oxygen and glucose deprivation during ischemia is a cause of tissue death. To prevent this, mammalian cells harbor protective biochemical mechanisms for minimizing ATP depletion during ischemia and episodes of high metabolic demand. The creatine kinase system is a key biochemical mechanism that prevents ATP depletion in mammalian cells.

COP's proposed entry into this system — via CK inhibition, phosphate donation, or creatine precursor activity — remains incompletely characterized at the molecular level in peer-reviewed literature independent of patent filings.

5. Body Systems and Health Areas Associated with COP

• Cardiovascular system: Anti-ischemic and anti-arrhythmic activity; positive inotropic effect in hypoxic conditions; membrane stabilization of cardiomyocytes; reduction of CK enzyme leakage in myocardial infarction.
• Skeletal muscle: Proposed enhancement of ATP availability; intracellular pH buffering; potential prolongation of anaerobic work capacity; one trial showing improved grip strength.
• Energy metabolism: Involvement in the creatine–phosphocreatine–ATP energy shuttle; possible creatine precursor activity.
• Renal system: COP and its metabolites are excreted renally; COP is well-absorbed intramuscularly, distributes in critical organs, and is dephosphorylated and excreted via the kidneys and liver.

6. Pharmacokinetics

Absorption

Oral administration in test animals has revealed that 2-(carbamimidoyl-methyl-amino)ethoxyphosphonic acid is optimally absorbed by the intestine up to about 60% at 48 [hours]. This figure — approximately 60% intestinal absorption — appears in patent literature (US Patent 7,375,097) and has not been independently confirmed in a formally published human pharmacokinetic study.

Distribution

Creatinol-O-phosphate is distributed in all organs, particularly in the liver and kidney, where it is dephosphorylated and eliminated with the urine.

Metabolism and Excretion

Based on findings that intravenous COP in healthy human subjects led to increased creatinine in urine, it is speculated that creatinol acts as a precursor of creatine and is metabolized into creatine within the body. The increased urinary values are derived from the degradation of creatine into creatinine through typical biochemical pathways.

Arterial pressure, heart rate, ECG pattern, and complete blood analysis showed no change at any COP dosage, with the exception of blood phosphate, which increased in the two higher-dose groups. Cumulative urinary excretion of phosphate and creatinine and diuresis increased, whereas other urine parameters did not change. The phosphate and creatinine increases derived from the COP molecule, and the increase in diuresis derived from a simple osmotic process required to dilute the phosphate in the tubular fluid.

7. Dosage Forms and Dosages Reported in Sources

The following dosages are reported strictly as they appear in identified source publications; they reflect investigational administration routes (predominantly intravenous and intramuscular) from the pharmaceutical research era, as well as one patent-reported figure for oral absorption. No oral dosage has been established in a published human clinical trial.

• Intravenous (acute tolerance study, healthy human volunteers): COP was administered intravenously at three different dosages: 1,020 mg (Group A), 2,040 mg (Group B), and 3,060 mg (Group C), compared with a placebo (Group D).
• Intramuscular and intravenous (muscular performance trial): Fifty female patients were treated intramuscularly and intravenously with COP. Specific dosage per administration was not retrievable in the available abstract.
• Oral (animal, patent report): Oral administration in test animals revealed that COP is optimally absorbed by the intestine up to about 60% at 48 hours. No mg/kg dose is explicitly cited in accessible sources for this figure.
• In vitro (isolated heart, mechanistic study): Aplodan at concentrations of 1–10 mM for 30 minutes decreased phosphocreatine and ATP signals in isolated hearts of Xenopus africanus in a ³¹P NMR spectroscopy study.
• Rat combination study (toxicology): In tests performed in rats, doses of L-carnitine and creatinol-phosphate in combination, corresponding to 250 mg/kg of each compound, were administered intraperitoneally without any signs of toxicity. No signs of toxicity were detected when 750 mg/kg of L-carnitine were administered orally in combination with 750 mg/kg of creatinol-phosphate.

8. Safety Considerations

General Toxicological Profile

The results of toxicological studies showed that creatinolfosfate did not have side effects. Toxicological studies confirm that COP is safe and well-tolerated, with a wide therapeutic index. These findings are based on studies published in the 1970s–1980s and on industry toxicology dossiers (e.g., Bibra International Ltd., Surrey, UK, 2002, "Toxicity Profile: Creatinol O-phosphate and its sodium salt"), rather than on modern GLP-compliant toxicological packages.

Both the carnitines and creatinol-phosphate are products known for their low toxicity and good tolerability. Even prolonged oral administration for one month of 200 mg/kg of L-carnitine plus 200 mg/kg of creatinol-phosphate to rats did not cause any toxic intolerance reaction. Full blood counts and blood-chemistry tests performed at the end of treatment also failed to reveal any abnormalities worthy of note compared to controls. At autopsy, none of the main organs showed any signs of distress. Histological and histochemical investigations confirmed these findings.

Clinically Observed Effects in Human Tolerance Study

Arterial pressure, heart rate, ECG pattern, and a complete blood analysis showed no change at any COP dosage, with the exception of blood phosphate, which increased in groups receiving 2,040 mg and 3,060 mg intravenously. The virtual absence of side effects of COP was noted by investigators in the arrhythmia double-blind trial.

Interactions: Creatine Kinase System

At the tissue level — i.e., muscle — through its protective effect, COP prevents the increase in CK levels occurring during muscle damage such as myocardial infarction or high-intensity exercise, which reflects the leakage of CK from the cytoplasm of damaged cells into the bloodstream. This property implies a potential pharmacodynamic interaction with other agents that affect the CK–phosphocreatine system, including therapeutic creatine, though no interaction studies have been formally published.

Phosphate Elevation and Renal Considerations

Because COP is a phosphonate compound and is excreted renally with accompanying phosphaturia, there is a theoretical consideration regarding individuals with impaired renal phosphate handling. Blood phosphate increased in the two higher-dose groups (2,040 mg and 3,060 mg IV) in the acute tolerance study. The principal human tolerance study specifically excluded subjects with "heart or renal disease and other serious illness," meaning safety data in renally impaired individuals are absent from the published record.

Regulatory and Labeling Status

The compound is noted as "possibly marketed outside the US" by the NIH NCATS database, consistent with its documented European pharmaceutical history under the trade name Aplodan. In the United States, it appears in sports nutrition supplement products as a dietary ingredient rather than as a licensed pharmaceutical product. Its primary use is in sports nutrition and functional sports beverages; some clinical/medical research explores cardioprotective or metabolic applications in specialty therapeutic contexts. No GRAS (Generally Recognized as Safe) notification, NDI (New Dietary Ingredient) notification, or approved drug application for COP has been identified in the accessible public record for the United States market as of the available literature.

Limitations of the Safety Data

All published safety data for COP derive from small, decades-old studies using parenteral (intravenous or intramuscular) administration in clinical patients or from animal experiments. COP's mechanisms and long-term effects require further investigation to fully establish its benefits and optimal usage. No long-term human safety trial of oral COP supplementation has been identified in any accessible peer-reviewed database. Absence of documented harm in the published record does not equate to established safety under contemporary regulatory standards.

9. Summary of Evidence Quality

The peer-reviewed body of evidence for COP can be summarized as follows:

• Cardiovascular (human clinical): Small double-blind trials (total enrolled patients: fewer than 50 across all trials) conducted in the late 1970s, all using parenteral administration, with vehicle-only comparators, in clinical (not healthy) populations. Evidence is preliminary and insufficient to establish efficacy by modern standards.
• Muscular performance (human clinical): A single controlled clinical trial (n = 50 women, parenteral administration) showing improved grip strength. No oral supplementation trials have been published in healthy or athletic populations. Evidence is very limited.
• Antiarrhythmic (human clinical): One small double-blind trial showing reduction of ventricular premature beats in patients with ischemic heart disease. Preliminary; not replicated.
• Mechanism studies (animal and in vitro): Multiple studies supporting positive inotropic effects, membrane stabilization, cardioprotection against ischemia/reperfusion injury, and anti-arrhythmic properties in isolated tissue and animal models. These provide biological plausibility but cannot be directly extrapolated to human supplementation outcomes.
• Overall: Scientific studies on COP are relatively limited, especially in the context of sports nutrition. The compound's entry into the consumer sports supplement market has significantly outpaced the human clinical evidence base.

References

• US Patent 7,375,097 — Increasing ATP Availability by Inhibition of Creatine Kinase (CK) Leakage Resulting from High-Intensity Exercise (Aplodan Formulations Ltd.)
• Barlattani M et al. Creatinol O-phosphate therapy in patients with inadequate coronary circulation. Double-blind clinical trial. Arzneimittelforschung. 1979;29(9a):1483–5. PubMed PMID: 395958
• Di Maio F et al. Activity of creatinol O-phosphate on persistent ventricular premature beats in ischemic heart disease. Double-blind clinical trial. Arzneimittelforschung. 1979;29(9a):1488–90. PubMed PMID: 395959
• Botti G et al. Preliminary report on electrophysiological effectiveness of creatinol O-phosphate (COP) in human subjects. Arzneimittelforschung. 1979;29(9a):1491–4. PubMed PMID: 575499
• Melloni B et al. Acute clinical tolerance of creatinol O-phosphate. Arzneimittelforschung. 1979. PubMed PMID: 575490
• Nicaise J. Creatinol O-phosphate (COP) and muscular performance: a controlled clinical trial. Curr Ther Res Clin Exp. 1975;17(6):531–534. PubMed PMID: 808375
• Marchetti G et al. Effects of creatinol-O-phosphate (COP) on haemodynamics and cardiac metabolism in conscious and anaesthetized dogs. Arzneimittelforschung. 1978;28(10):1708–11. PubMed PMID: 582673
• Protective effect of creatinol O-phosphate (COP) on some experimental arrhythmias in vitro and in vivo. PubMed PMID: 575497
• Godfraind T, Saleh MM. Action of creatinol-O-phosphate on the contractility changes evoked by hypoxia and ischemia in rat isolated heart. Arzneimittelforschung. 1984;34(9):968–72. PubMed PMID: 6542374
• Jäger R et al. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. Amino Acids. 2011;40(5):1369–83. PMC3080578
• NIH NCATS Inxight Drugs — CREATINOLFOSFATE (5O564RN1QD)
• US Patent 6,602,512 — Composition for the Prevention of Muscle Fatigue and Skeletal Muscle Adaptation of Strenuous Exercise (Creatinol-phosphate + Carnitine combination)
• US Patent 4,376,117 — Creatinol-O-phosphates Having Therapeutical Action
• US Patent 8,372,821 — Stable Aqueous Compositions Comprising Bioactive Creatine Species
• US Patent Application 20140256987 — Creatinol O-phosphate and Synthesis Method Thereof
• Phosphatase activity of guinea-pig tissues on creatinol O-phosphate in vitro. Journal of Pharmacy and Pharmacology. 1972.
• Ellington WR. Relating structure to mechanism in creatine kinase. Biochemistry. 2005. PubMed PMID: 15804623