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Creatinol O-Phosphate

Creatinol O-Phosphate (COP) is a creatine analogue synthesized for the treatment of heart complications. It appears to protect cardiac cells at 3g injections, but does not have sufficient evidence for oral consumption.

Our evidence-based analysis on creatinol o-phosphate features 10 unique references to scientific papers.

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Research Breakdown on Creatinol O-Phosphate

1Sources and Structure


Creatinol O-Phosphate (also known as Creatinolphosphate or Aplodan[1]), sometimes abbreviated as COP, is a cardioprotective drug that appears to have been well researched a few decades ago and has since had a lack of recent studies.

The name of the molecular structure in full is N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate.[1] The molecule of COP is different than that of the phosphorylated form of creatine, as the phosphate group is attached to a different segment of the creatine molecule. COP has not yet been shown to carry the traditional benefits of creatine supplementation, and for practical purposes should be seen as a different molecule.



Creatinol-O-Phosphate injections appear to be distributed in all tissues with most concentrated in the myocardium, liver, and kidneys; being excreted (as creatinol) when dephosphorylated.[2]

3Cardiovascular Health

3.1Cardiac Tissue

100umol/L of COP can invoke a positive ionotropic effect that is glucose dependent and a slight negative chronotropic effect when oxygen is in the range of normoxia, and helped the recovery of cardiac contractility after ischemia (lack of oxygen) which is thought to be via a glycolytic mechanism.[1]

One study that used isoprenaline (beta-adrenergic agonist) in a dose that was able to induce cardiac lesions noted that pretreatment of 200mg/kg COP (injections) was able to significantly attenuate the degree of cardiac lesions[3] and doses up to 1000mg/kg have been shown to dose-dependently reduce death induced by an overdose of isoprenaline in mice (16% reduction at 250mg/kg, 50% reduction at 1000mg/kg).[4] Low doses can increase in efficacy over 4 days of loading when compared to the same dose taken 4 hours acutely prior to the isoprenaline insult,[5] and these effects may occur in a rehabilitative manner as evidence by 3060mg of Creatinol O-Phosphate given for three days (IV) to persons who recently suffered a Myocardial infarction, where serum cardiac enzymes decreased by 33-46% relative to control.[6]

Injections of Creatinol O-Phosphate have an apparent cardioprotective effect against beta-adrenergic induced lesions and may possibly be rehabilitative as well; no studies on oral ingestion at this time

A reduction in the time required for atropine to induce cardiac arrythmia in guinea pigs has also been noted.[4] Anti-arrythmic properties have been noted in vivo with COP supplementation[7] even after three days of 2040mg (twice daily 1020mg injections).[8]

Administration of COP, as well as the reference drug atropine, have been shown to improve A-V conduction of the heart in a small sample (n=6) pilot study; atropine's benefits were more evidence.[9]

Injections of COP appear to be beneficial for arrythmia disturbances, no studies on oral ingestion

4Safety and Toxicity

In rats, injections of up to 1000mg/kg appear to not be associated with death acutely[4]

In otherwise healthy humans, intravenous doses of up to 3060mg COP failed to alter Arterial pressure, heart rate, ECG pattern, or all aspects aside from phosphorus levels (which increased following 2040-3060mg) in a blood panel; an increase in urinary phosphorus and diuresis also resulted with no overt signs of toxicity.[10]

Currently appears to be safe following injections of up to around 3g, no studies conducted on oral administration