Coluracetam
[CAS# 135463-81-9]

Identification

• Classification: API >> Nervous system medication >> Brain metabolism regulating drug
• Name: Coluracetam
• Synonyms: N-(2,3-Dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)-2-(2-oxopyrrolidin-1-yl)acetamide
• Molecular Formula: C₁₉H₂₃N₃O₃
• Molecular Weight: 341.40
• CAS Registry Number: 135463-81-9
• SMILES: CC1=C(OC2=NC3=C(CCCC3)C(=C12)NC(=O)CN4CCCC4=O)C

Properties

• Solubility: <1 mg/mL (water), 47 mg/mL (DMSO), 47 mg/mL (ethanol) (Expl.)
• Density: 1.3±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.641, Calc.^*
• Boiling Point: 634.1±55.0 ºC (760 mmHg), Calc.^*
• Flash Point: 337.3±31.5 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

Coluracetam, chemically known as 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)acetamide, is a nootropic compound belonging to the racetam family. Originally developed in Japan in the 1990s by Mitsubishi Tanabe Pharma Corporation as a potential treatment for Alzheimer’s disease, its cognitive-enhancing properties have made it an area of interest in neuropharmacology.

The discovery of coluracetam stems from efforts to develop novel treatments for neurodegenerative diseases. Mitsubishi conducted initial studies to explore its effects on cognitive deficits in Alzheimer’s patients. Though these trials did not lead to further development for Alzheimer’s, the compound exhibited promising neuroprotective and cognitive-enhancing properties, sparking continued research into its applications.

Coluracetam functions primarily by modulating high-affinity choline uptake (HACU) in the brain. This mechanism is crucial for acetylcholine synthesis, a neurotransmitter essential for learning, memory, and other cognitive processes. Unlike other racetams, coluracetam appears to enhance HACU even under conditions of neuronal stress, such as glutamate-induced toxicity, which has implications for neuroprotection.

One of the main applications of coluracetam is its potential as a nootropic. Preliminary studies suggest it may improve memory, learning capacity, and focus, particularly in individuals with cognitive impairments. In animal models, coluracetam has demonstrated the ability to improve retention and recall in memory-deficient subjects, further supporting its role as a cognitive enhancer.

In addition to its nootropic properties, coluracetam has been investigated for its potential in treating mood disorders. Some studies suggest that it may have antidepressant-like effects, likely through its impact on cholinergic activity and modulation of glutamate receptors. This makes it a candidate for further exploration in the treatment of conditions like major depressive disorder and anxiety.

Neuroprotection is another area of interest for coluracetam. Its ability to sustain acetylcholine synthesis under stress suggests potential applications in neurodegenerative conditions, traumatic brain injuries, and ischemic events. These properties align with the broader goals of neurotherapeutics aimed at preserving cognitive function and preventing neuronal loss.

Despite its promising profile, coluracetam remains underexplored in human clinical trials. Much of the evidence for its efficacy and safety comes from preclinical studies and anecdotal reports. Challenges such as limited bioavailability and a lack of comprehensive pharmacokinetic data hinder its broader application in medicine.

Coluracetam has gained attention in the nutraceutical industry as a dietary supplement marketed for cognitive enhancement and mood improvement. However, its use in this context is not regulated, and more rigorous studies are needed to validate its purported benefits and ensure safety.

In summary, coluracetam represents a unique approach to cognitive and neuroprotective therapy through its modulation of choline uptake and acetylcholine synthesis. While its potential applications are vast, further research is necessary to establish its clinical utility and optimize its use in neuropharmacology.