Cyclocreatine is a synthetic compound that has garnered scientific attention due to its structural similarity to creatine, a naturally occurring molecule involved in cellular energy. It is considered a “creatine analog,” meaning it mimics creatine’s biological actions while possessing unique properties. Researchers are exploring cyclocreatine for its potential in various biological contexts, particularly those involving energy metabolism and cellular protection.
Chemical Structure and Relation to Creatine
Cyclocreatine distinguishes itself from creatine by its cyclic chemical structure. While creatine has an open-chain guanidino group, cyclocreatine incorporates this group into a five-membered ring, a 2-iminoimidazolidine ring, with an acetic acid group attached. This structural difference, particularly its planar configuration, allows cyclocreatine to passively cross cell membranes, including the blood-brain barrier, which is an advantage for potential therapeutic applications in the brain.
The formal name for cyclocreatine is 2-amino-4,5-dihydro-1H-imidazole-1-acetic acid, also known as 1-Carboxymethyl-2-iminoimidazolidine or AM 285. Its molecular formula is C5H9N3O2, with a molecular weight of 143.15. This subtle yet important structural modification influences how cyclocreatine interacts with biological systems compared to its natural counterpart.
Mechanism of Action
Cyclocreatine exerts its effects by interacting with the creatine kinase (CK) system, which is central to cellular energy buffering. Like creatine, cyclocreatine can be phosphorylated by creatine kinases, forming cyclocreatine phosphate (CCrP). This phosphorylation process is reversible and occurs in both mitochondrial and cytosolic creatine kinases.
Cyclocreatine phosphate acts as a “phosphagen analog,” functioning as a high-energy phosphate buffer. It can donate its phosphate group to adenosine diphosphate (ADP) to rapidly regenerate adenosine triphosphate (ATP), the primary energy currency of the cell. This process helps maintain ATP levels, particularly in tissues with high and fluctuating energy demands, such as the brain and muscles. Studies in the mouse brain have shown cyclocreatine phosphorylation to be higher than phosphocreatine, suggesting a strong buffering capacity.
Research Directions and Potential Uses
Scientific research on cyclocreatine explores its potential in various conditions, largely stemming from its ability to influence cellular energy metabolism. It has been investigated for its neuroprotective effects, particularly in models of neurodegenerative diseases like Huntington’s disease and Alzheimer’s disease. In mouse models of creatine transporter deficiency, cyclocreatine treatment has shown promise in ameliorating cognitive deficits by providing an alternative energy buffer.
Cyclocreatine is also being examined for its anti-tumor properties. Studies indicate it can suppress creatine metabolism and inhibit the proliferation of prostate cancer cells, potentially by reducing intracellular levels of creatine and its derivatives. Additionally, cyclocreatine has shown promise in protecting against ischemic injury and enhancing cardiac recovery during early reperfusion in animal models of myocardial infarction, suggesting a potential role in cardiovascular diseases by preserving myocardial ATP during periods of low oxygen.
Current Status and Safety Considerations
Cyclocreatine is primarily a compound used in scientific research and is not a widely available consumer product or dietary supplement. It is sold for “research use only” and is not intended for human or veterinary use.
Information on its safety profile in humans is limited, as it has mainly been studied in animal models. Chronic administration of cyclocreatine in Sprague Dawley rats at higher doses (e.g., 600 mg/kg/day) has been reported to induce seizures and microscopic lesions in the brain, testes, and thyroid. Thyroid follicular atrophy and seminiferous tubular degeneration were observed at doses of 200 mg/kg/day and higher in males. These findings highlight the need for careful evaluation of dosage and potential side effects in any future human studies.