1.
Sources and Structure
1.1
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.
2.
Pharmacology
2.1
Excretion
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]
3.
Cardiovascular Health
3.1
Cardiac 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
4.
Safety 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
References
- ^Godfraind T, Saleh MMAction of creatinol-O-phosphate on the contractility changes evoked by hypoxia and ischemia in rat isolated heartArzneimittelforschung.(1984)
- ^Marzo A, Ghirardi PPharmacological and toxicological properties of creatinol O-phosphate. A reviewArzneimittelforschung.(1979)
- ^Godfraind T, Sturbois XThe prevention by creatinol O-phosphate of myocardial lesions evoked by isoprenalineArch Int Pharmacodyn Ther.(1979 Feb)
- ^Ferrini R, Miragoli GProtective effect of creatinol O-phosphate (COP) on some experimental arrhythmias in vitro and in vivoArzneimittelforschung.(1979)
- ^Godfraind T, Sturbois XAn analysis of the reduction by creatinol O-phosphate of the myocardial lesions evoked by isoprenaline in the ratArzneimittelforschung.(1979)
- ^Knippel M, Bana G, Pusterla GLEffects of creatinol O-phosphate on serum enzymes in acute myocardial infarctionArzneimittelforschung.(1979)
- ^Di Maio F, Neri A, Soccorsi P, Sciacca AActivity of creatinol O-phosphate on persistent ventricular premature beats in ischemic heart disease. Double blind clinical trialArzneimittelforschung.(1979)
- ^Cadel A, Palumbo A, Zerilli G, Pria R, Fanciulli R, Conversano S, Galbiati RAntiarrhythmic effectiveness of creatinol O-phosphate in manArzneimittelforschung.(1979)
- ^Botti G, Bonatti VPreliminary report on electrophysiological effectiveness of creatinol O-phosphate (COP) in human subjectsArzneimittelforschung.(1979)
- ^Melloni GF, Minoja GM, Lureti GF, Merlo L, Pamparana F, Brusoni BAcute clinical tolerance of creatinol O-phosphateArzneimittelforschung.(1979)