Acts as a partial agonist of central GABA_A receptors. Modifies NMDA receptor activity. Related to serotonin and dopamine systems. [1]

In hippocampal brain slices, application of creatine enhanced synaptic plasticity. This effect was not observed in the presence of AP5, an NMDA receptor antagonist. [1]
Depolarization of rat brain tissue produced an influx of Ca²⁺ and subsequent release of creatine in an excitotoxic, action-potential dependent manner. Release was blocked in the absence of Ca²⁺ or when Na⁺ channels were blocked by tetrodotoxin. [1]
Creatine prevents oxidative damage through direct antioxidant activity in mammalian cell cultures. [1]

In female rats, daily supplementation with 4% creatine in the diet for five weeks produced antidepressant-like effects in the forced swim test. Sub-acute treatment with low-dose fluoxetine augmented this effect. In male rats under the same protocol, increased depression-like behavior was observed. [1]
In an open-label clinical trial, daily supplementation with 3-5 g creatine for four weeks improved mood in adult patients with treatment-resistant depression. [1]
In another open-label, add-on study, 4 g of creatine daily for 8 weeks improved depressive symptoms and increased brain phosphocreatine concentrations in treatment-resistant female adolescents concurrently prescribed the SSRI fluoxetine. [1]
Preliminary open-label studies reported improved symptoms in patients with treatment-resistant post-traumatic stress disorder (PTSD) following creatine supplementation. A case study also reported improvements in a patient with PTSD, depression, and fibromyalgia. [1]
A randomized, double-blind crossover study found creatine supplementation was not superior to placebo in treating symptoms of schizophrenia. [1]
Case reports suggest creatine supplementation might have precipitated manic episodes in two subjects with bipolar disorder approximately three weeks post-treatment. [1]
In healthy volunteers, creatine supplementation reduced mental fatigue following a stressful calculation test, improved working memory and intelligence scores in vegetarians, and buffered age-related cognitive decline in older adults. [1]
In rodent models of cognition, female mice supplemented with 1% creatine performed better on object recognition tests. Intra-hippocampal administration of creatine in male rats improved spatial learning in the Barnes Maze test. [1]
Young chickens that had creatine administered directly into their brains prior to social separation displayed significantly fewer stress responses. This effect was blocked by concomitant administration of picrotoxin, a GABA_A antagonist. [1]

In a rodent model of antidepressant efficacy, rats were supplemented with a diet containing 4% creatine for five weeks. Behavioral despair was then assessed using the forced swim test. [1]
In a study on cognition, female mice were supplemented with 1% creatine in their diet and later tested on the object recognition task. Male rats received intra-hippocampal administration of creatine at doses of 2.5 and 7.5 mmol and were assessed for spatial learning using the Barnes Maze test. [1]
To study stress responses, young chickens received an intracerebral administration of creatine (2 μg) prior to being subjected to social separation. Stress responses like vocalizations and plasma corticosterone levels were measured. [1]
In human clinical trials for depression and PTSD, oral creatine monohydrate was typically administered at doses ranging from 3 to 5 g per day, over periods of 4 to 8 weeks, often as an add-on to existing psychotropic medications. [1]

Creatine can be absorbed from the diet or synthesized endogenously in the kidneys, liver, and pancreas. After ingestion or biosynthesis, creatine enters tissues, including the brain, via specific sodium chloride-dependent creatine transporters (CRTs). [1]
Creatine enters the brain more slowly than it enters muscles due to the structural limitations of the blood-brain barrier. [1]
Daily supplementation with creatine monohydrate (e.g., 5 grams four times a day for four weeks) reliably increases brain creatine and phosphocreatine levels, with the most significant effects after several weeks. [1]
It is speculated that lower doses of creatine (less than 5 grams in humans) have higher bioavailability than higher doses (more than 10 grams), possibly due to saturation of the transport mechanism. [1]
Tissues with low creatine concentrations before supplementation (e.g., vegetarians) accumulate more creatine after supplementation. [1]
The absolute bioavailability of supraphysiological doses of creatine is unknown. Factors that may reduce bioavailability include gastric degradation, intestinal bacterial degradation, and incomplete dissolution. [1]

Creatine supplementation is generally considered safe and well-tolerated in humans and animals at recommended doses (e.g., 5 g daily for healthy adults). [1] Mild to moderate side effects reported include gastrointestinal discomfort (diarrhea, nausea, vomiting, abdominal discomfort), weight gain (due to water retention), and dehydration (although empirical evidence on dehydration is limited). [1] While some case reports suggest renal impairment, most studies suggest that creatine may exacerbate pre-existing kidney disease in healthy individuals rather than cause it. Elevated serum creatinine levels caused by creatine supplementation may be mistaken for renal impairment. [1] A few human trials and one animal study have documented negative changes in mood or anxiety. Specifically, case reports have indicated hypomania or mania in patients with bipolar disorder, with some subjects experiencing increased aggression or tension. Increased depressive-like behavior was observed in male rats supplemented with creatine. [1] Few studies have carefully investigated side effects at daily doses exceeding 5 g. [1]

[1]. Allen, P.J., Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value. Neurosci Biobehav Rev, 2012. 36(5): p. 1442-62.

[2]. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med, 2006. 145(4): p. 247-54.

Creatinine is a lactam formed from creatine via a cyclocondensation reaction and is a metabolite of creatine. It serves both as a diagnostic reagent and as a human metabolic product. Creatinine is a lactam and an imidazolidinone compound whose function is related to creatine. Creatinine has been used in clinical trials for the treatment of amyotrophic lateral sclerosis (ALS). It has been reported that creatinine is found in pomegranate (Punica granatum), mulberry bark (Morus alba), and other organisms with relevant data. Creatinine is a breakdown product of creatine, a component of muscle tissue, and is excreted by the kidneys; its serum levels can be used to assess kidney function. Creatine is a natural compound that plays an important energy buffering role in high-energy-demand tissues such as muscles and the brain. Its main function is to maintain cellular energy homeostasis through the creatine/phosphocreatine/creatine kinase system, which rapidly regenerates ATP. [1]
Changes in brain creatine metabolism have been observed in a variety of mental illnesses, such as schizophrenia, bipolar disorder, depression, and anxiety disorders. These changes typically occur in the frontal lobe and limbic system regions, but the direction of the changes is not consistent. These changes may represent an overall metabolic defect. [1]
The potential of creatine in the treatment of mental illnesses may involve multiple mechanisms: restoring cellular energy metabolism, exerting antioxidant effects, neuromodulation (affecting the GABAergic, glutamatergic, and monoaminergic systems), and increasing the availability of SAMe by reducing the consumption of S-adenosylmethionine (SAMe), which is required for endogenous creatine synthesis. [1]
Responses to creatine supplementation may differ between sexes. Women (including humans and rodents) may exhibit different metabolic characteristics and treatment responses compared to men. [1]
Psychoactive drugs (such as antidepressants, antipsychotics, mood stabilizers, and electroconvulsive therapy) have been shown to alter the activity of creatine, phosphocreatine, or creatine kinase in the brain, suggesting an interaction between these treatments and creatine metabolism. [1]
Methodological challenges include small sample size, diagnosis of comorbidities, concomitant medications, and the use of creatine as an internal standard in magnetic resonance spectroscopy (MRS), which complicates the interpretation of creatine levels in patients with mental illness. [1]

C4H7N3O

113.1179

113.058

60-27-5

60-27-5 (Creatinine); 616-04-6 (N-Methylhydantoin, a product of degradation of creatinine by bacteria); 61-47-2 (5-Hydroxytryptamine creatinine sulfate monohydrate); 143827-20-7 (Creatinine-D3)

588

White to off-white solid powder

1.5±0.1 g/cm3

184.3±23.0 °C at 760 mmHg

295 °C (dec.)(lit.)

65.3±22.6 °C

0.2±0.8 mmHg at 25°C

1.651

-1.68

1

1

0

8

151

0

DDRJAANPRJIHGJ-UHFFFAOYSA-N

InChI=1S/C4H7N3O/c1-7-2-3(8)6-4(7)5/h2H2,1H3,(H2,5,6,8)

2-Imino-1-methylimidazolidin-4-one

NSC 13123; NSC-13123; NSC13123

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)