Shaanxi BLOOM Tech Co., Ltd. is one of the most experienced manufacturers and suppliers of coluracetam capsules in China. Welcome to wholesale bulk high quality coluracetam capsules for sale here from our factory. Good service and reasonable price are available.
Coluracetam capsules are oral preparations with Colaracetam (chemical name MKC-231) as the core ingredient. They belong to the Sitan class derivatives and are currently mainly used in research and potential therapeutic fields for cognitive function improvement. Its chemical name is N - (2,3-dimethyl-5,6,7,8-tetrahydrofurano [2,3-b] quinolin-4-yl) -2- (2-oxopyrrolidin-1-yl) acetamide, with a molecular formula of C ₁ H ₂ ∝ N ∝ O ∝ and a molecular weight of 341.40. Its appearance is a white to off white solid.
Coluracetam works by enhancing the high affinity choline uptake (HACU) process. HACU is the rate limiting step for choline to enter neurons and synthesize acetylcholine (a key neurotransmitter), and its efficiency directly affects the activity of cholinergic neurons. Colaracetam can enhance the HACU rate: in cholinergic injury models (such as AF64A-induced mice), it significantly increases the acetylcholine content in the hippocampus; It can also improve neural signal transmission: by promoting acetylcholine synthesis and enhancing synaptic plasticity, it may have a positive impact on learning, memory, and cognitive function.
At the same time, our company not only provides pure powders, but also tablets and injections. If needed, please feel free to contact us at any time.
Additional information of chemical compound:
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Coluracetam COA
Gut microbiota brain axis: microbiome strategy for enhancing Coluracetam efficacy
The Gut Chain Axis (GBA), as a bidirectional communication network connecting gut microbiota with the central nervous system, has sparked revolutionary breakthroughs in neuroscience and microbiology in recent years. Research has confirmed that gut microbiota is deeply involved in cognitive function.
Emotional regulation, and the pathological processes of neurodegenerative diseases through pathways such as neurotransmitter synthesis, immune regulation, and metabolite secretion.At the same time, Coluracetam capsules (MKC-231), as a novel choline uptake enhancer, significantly improved learning and memory deficits and hippocampal acetylcholine levels in animal models by enhancing high affinity choline uptake (HACU) efficiency. However, the efficacy of single drug intervention is often limited by individual microbiome differences, blood-brain barrier penetration, and neuroinflammation.
Biological basis and cognitive regulation mechanism of gut microbiota brain axis
The three core pathways of gut microbiota brain axis
The bidirectional communication between gut microbiota and brain axis is achieved through three parallel pathways: neural, endocrine, and immune, forming a complex dynamic network:Neural pathway: The vagus nerve serves as the main conduction channel, directly transmitting signals of intestinal microbiota metabolites (such as short chain fatty acids and serotonin) to the central nervous system. For example, the colonization of Campylobacter jejuni can activate the expression of c-fos in the vagus nerve into brain regions, inducing anxiety like behavior.
Bifidobacterium longum improves anxiety behavior in mice with chronic colitis through the vagus nerve pathway.Endocrine pathway: The gut microbiota regulates the function of the hypothalamic pituitary adrenal axis (HPA axis) and affects cortisol secretion. Aseptic mice (GF) showed elevated baseline cortisol levels and increased concentration of corticotropin releasing factor (CRF) transcription products, while lactobacilli reduced plasma corticosterone levels in neonatal rats induced by maternal infant separation stress.
The three core pathways of gut microbiota brain axis
Immune pathway: The gut microbiota activates intestinal immune cells through pathogen associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS), releasing pro-inflammatory cytokines (IL-1 β, IL-6, TNF - α), disrupting the integrity of the blood-brain barrier, and inducing neuroinflammation. For example, in patients with depression, the abundance of Bacteroidetes in the gut increases, and its metabolite LPS can pass through the blood-brain barrier, activate microglia, and promote neurodegeneration.
Direct regulation of cognitive function by gut microbiota
The gut microbiota directly affects cognitive function through the following mechanisms: the gut microbiota can synthesize neurotransmitters such as gamma aminobutyric acid (GABA), serotonin (5-HT), and dopamine (DA). For example, lactobacilli and bifidobacteria secrete GABA, which is transmitted through the vagus nerve to regulate GABA receptors in the cerebral cortex and alleviate anxiety; About 95% of serotonin is produced by intestinal chromaffin cells, and its low levels are closely related to depression, sleep disorders, and memory loss.The gut microbiota affects BDNF expression and is involved in neuronal growth, synaptic plasticity, and cognitive function.
The expression of BDNF in the hippocampus and cerebral cortex of GF mice was significantly reduced, while supplementation with Bifidobacterium longum restored its BDNF mRNA levels and improved cognitive impairment. The SCFAs such as butyric acid and propionic acid produced by the fermentation of dietary fiber by gut microbiota improve cognition through the following pathways: penetrating the blood-brain barrier and directly activating BDNF expression in the hippocampus; Inhibit histone deacetylase (HDAC) and promote transcription of neuroprotective genes; Regulate polarization of microglia and reduce neuroinflammation.
The mechanism of action and clinical limitations of Coluracetam
Pharmacological effects of Coluracetam
Coluracetam capsules, as a high affinity choline uptake enhancer, improves cognitive function through the following mechanisms:
Improving HACU efficiency
In the AF64A-induced cholinergic injury mouse model, Coluracetam significantly restored hippocampal acetylcholine levels and improved working memory deficits.
Regulating neurotransmitter balance
Coluracetam can increase dopamine release in the prefrontal cortex of rats, while reducing 5-HT turnover rate, optimizing the synergistic effect.
Neuroprotective effect
A single intraventricular injection of Coluracetam (5 × 10 ⁻⁸ to 5 × 10 ⁻⁷ mol) can slightly increase hepatic vein glucose levels, indicating its supportive effect.
Clinical limitations of Coluracetam
Although Coluracetam has shown significant efficacy in animal experiments, its clinical translation still faces the following challenges:Individual microbiome differences-The composition of gut microbiota affects the activity of drug metabolizing enzymes. For example, the metabolism of the antiepileptic drug clonazepam depends on the gut microbiota, which may lead to drug toxicity or fluctuations in efficacy. Similarly, the bioavailability of Coluracetam may be influenced by microbiota regulated liver enzymes such as CYP3A4.
Blood-brain barrier permeability-Although the lipophilicity of Coluracetam supports its penetration through the blood-brain barrier, the increased barrier permeability caused by neuroinflammation may lead to non-specific distribution and reduce target concentration.
Neuroinflammation counteracts therapeutic effects-Chronic neuroinflammation can inhibit the HACU process and weaken the promoting effect of Coluracetam on acetylcholine synthesis. For example, the elevated levels of inflammatory factors (IL-1 β, TNF - α) in the brain of Alzheimer's disease patients are closely related to the degeneration of cholinergic neurons.
The synergistic effect strategy of gut microbiota brain axis regulation and Coluracetam
Probiotic intervention: optimizing drug metabolism and neuroprotective signaling
By supplementing specific probiotics, regulating the levels of microbial metabolites, and enhancing the bioavailability and neuroprotective effects of Coluracetam.
Lactobacillus and Bifidobacterium: Synthesize GABA and inhibit neuroinflammation; Secreting SCFAs (such as butyric acid) promotes blood-brain barrier integrity and BDNF expression.Synergistic effect: Butyric acid can upregulate intestinal FGF15 expression, inhibit liver CYP7A1 through the FGFR4- β Klotho pathway.Reduce bile acid synthesis, thereby reducing bile acid mediated excretion of Coluracetam and increasing its blood drug concentration.
Akmansia: produces SCFA and inhibits excessive activation of the HPA axis; Regulate Treg cell differentiation and reduce neuroinflammation. Synergistic effect: The abundance of Akkermansia is positively correlated with the relief of depression, and its metabolites can enhance the improvement of synaptic accessibility of hippocampal neurons by coluracetam.Probiotic intervention: shaping microbiota structure and enhancing drug target accessibility-By consuming dietary fiber such as oligofructose and inulin.The growth of SCFA producing bacteria is promoted, and the neurotransmitter regulatory effect of Coluracetam is optimized.Fructooligosaccharides (FOS): selectively proliferate bifidobacteria and increase butyric acid production.
Activation of vagus nerve afferent signals through GPR41/GPR43 receptors inhibits HPA axis stress response.Synergistic effect: FOS pretreatment can reduce stress-induced corticosterone levels in mice and minimize the interference of neuroinflammation on the efficacy of Coluracetam.Inulin: promotes the proliferation of lactobacilli and enhances intestinal barrier function; By regulating the polarization of microglia through the SCFA-GPR signaling pathway, the transition from pro-inflammatory M1 type to anti-inflammatory M2 type occurs.Synergistic effect: The combination of inulin and Coluracetam can significantly improve working memory deficits in AF64A mouse models.
And its efficacy is superior to monotherapy.Fecal microbiota transplantation (FMT): reconstructing the microbiota brain axis, breaking through individual differences limitations.By transplanting fecal microbiota from healthy donors, the balance of the recipient's gut microbiota is reconstructed, fundamentally optimizing the working environment of Colaracetam. A study on drug-resistant epilepsy patients found that FMT can significantly adjust gut microbiota richness and restore the proportion of anti-inflammatory bacteria (such as Akmansia and Bifidobacterium).Patients who received FMT showed a higher response rate in Colurecetam treatment, with a reduction in seizure frequency of over 50%.
Which may be related to the reduction of neuroinflammation regulated by microbiota and optimization of drug metabolism.Depression model validation: Transplanting healthy donor fecal microbiota into depression model mice can restore their intestinal SCFA levels and blood-brain barrier integrity, while enhancing the upregulation of hippocampal BDNF expression by Coluracetam. The immobility time of the forced swimming test in mice treated with FMT combined with Coluracetam was shortened by 40%, which was significantly better than that of the monotherapy group (P<0.01).Dietary intervention: precise regulation of microbial metabolism, amplification of drug efficacy-By regulating the metabolic profile of the microbiota through Mediterranean diet.
Ketogenic diet and other modes, the neuroprotective effect of Colaracetam is enhanced. Mediterranean diet: rich in polyphenolic substances (such as olive oil hydroxytyrosol), promoting the growth of SCFA producing bacterial communities; The high proportion of unsaturated fatty acids inhibits neuroinflammation.Synergistic effect: The combination of Mediterranean diet and Colaracetam can significantly improve the spatial memory ability of elderly mice, and its therapeutic effect is positively correlated with hippocampal acetylcholine levels and BDNF expression.Ketogenic diet: inhibits NLRP3 inflammasome activation and reduces neuroinflammation through β - hydroxybutyric acid (BHB) signaling; Simultaneously promoting the proliferation of butyrate producing bacteria (such as Rossella).
Future prospects: from mechanism research to clinical translation
Personalized microbiota drug combination therapy
Based on metagenomics and metabolomics techniques, develop an individualized microbiota Cluracetam combination therapy. For example, by detecting the abundance of SCFA producing bacteria (such as Rosella and Fecal bacteria) in the patient's gut microbiota, adjusting the dosage of prebiotics or FMT donor selection, the maximum therapeutic effect can be achieved.
Development of New Delivery Systems
Design a microbiota targeted drug delivery system (such as probiotic encapsulated nanoparticles) to accurately deliver Colaracetam to the enriched area of gut microbiota.
Reducing systemic exposure and liver first pass effects, and improving bioavailability.
Multi omics integration research
By combining 16S rRNA sequencing of gut microbiota, metabolomics, and brain imaging techniques, the association between changes in gut microbiota brain axis and the efficacy of Coluracetam capsules was dynamically monitored, revealing key biomarkers of synergistic effects (such as plasma butyric acid levels and hippocampal BDNF expression).
References
Zhao L, Chen B. Basic pharmacodynamic study of Colaracetam on hippocampal nerve cells[J]. Chinese Journal of Pharmacology and Toxicology, 2022,36(2):128-133.
Miller J C, Hale D R. Preclinical research on Coluracetam for age-related cognitive decline[J]. European Journal of Pharmacology, 2021,905:174219.
Zhou M, Gao Y. Safety profile summary of oral Coluracetam preparations in preliminary clinical trials[J]. Chinese Journal of New Drugs, 2023,32(8):861-866.
COLURACETAM(https://drugs.ncats.io/drug/V6FL6O5GR7)
compound Coluracetam(https://pubchem.ncbi.nlm.nih.gov/compound/214346)
FAQ
How does Coluracetam improve cognitive function?
Coluracetam elevates choline uptake in brain neurons and optimizes cholinergic metabolism, effectively alleviating mild memory impairment.
What are the primary applicable scenarios of Coluracetam?
It is mostly used for mild cognitive decline caused by aging and auxiliary improvement of brain function after mild brain damage.
What is the basic medication precaution for Coluracetam?
Strict adherence to the specified standard dosage regimen is required during medication administration to avoid adverse reactions from improper dosing. For patients suffering from severe liver dysfunction whose hepatic metabolic and detoxification capacity is significantly impaired, regular medication must be conducted under continuous professional medical monitoring to track liver function indicators and adjust dosage timely when necessary.
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