Nefiracetam
Descripción general
Descripción
Nefiracetam es un compuesto nootrópico que pertenece a la familia de las racetamas. Fue desarrollado por primera vez en Tokio en la década de 1990 por Daiichi Pharmaceutical. This compound es conocido por sus propiedades de mejora cognitiva, incluyendo mejoras en la memoria, el estado de ánimo y la motivación. Es un derivado del piracetam, con una estructura química similar pero con un grupo fenilo y dos grupos metilo añadidos a la amina, lo que aumenta su potencia en comparación con otras racetamas .
Aplicaciones Científicas De Investigación
Pharmacological Mechanisms
Nefiracetam exhibits several pharmacological actions that contribute to its nootropic effects:
- Cholinergic System Modulation : this compound enhances the activity of nicotinic acetylcholine receptors, which are crucial for cognitive functions such as learning and memory. It interacts with a protein kinase C pathway, promoting acetylcholine turnover and release .
- Glutamatergic System Interaction : Research indicates that this compound potentiates N-methyl-D-aspartate (NMDA) receptor currents, enhancing synaptic transmission and potentially improving cognitive function .
- GABAergic Activity : this compound shows high affinity for GABA A receptors, suggesting it may function as an agonist, which could help mitigate anxiety-related symptoms .
Alzheimer's Disease
This compound has been investigated for its potential in treating Alzheimer's disease. A double-blind, placebo-controlled trial aims to assess its efficacy in improving cognitive function among patients with mild to moderate dementia. The study utilizes standardized neuropsychological tests to evaluate outcomes .
Post-Stroke Rehabilitation
This compound has been evaluated for its effects on post-stroke apathy. A randomized controlled trial involving 13 patients found no significant difference between this compound and placebo in reducing apathy scores . Despite this, there is ongoing interest in its potential benefits for cognitive recovery post-stroke .
Antiepileptic Potential
In animal models, this compound has demonstrated anticonvulsant properties by reducing the severity and duration of seizures induced by amygdala kindling. This suggests a potential application in epilepsy management .
Case Studies and Research Findings
| Study Title | Sample Size | Findings | |
|---|---|---|---|
| Efficacy of this compound in Alzheimer's Disease | TBD | Evaluated cognitive improvement through neuropsychological tests | Ongoing study; results pending |
| This compound for Post-Stroke Apathy | 13 | No significant difference compared to placebo | Limited efficacy; highlights need for larger trials |
| Anticonvulsant Effects in Rats | TBD | Reduced seizure severity and duration in kindled rats | Suggests potential for epilepsy treatment |
Mecanismo De Acción
Nefiracetam ejerce sus efectos a través de múltiples mecanismos:
Sistema GABAérgico: Mejora la señalización GABAérgica modulando los receptores GABA.
Sistema colinérgico: Aumenta los niveles de acetilcolina potenciando los receptores nicotínicos de acetilcolina.
Sistema monoaminérgico: Modula los neurotransmisores monoamina como la dopamina y la serotonina.
Canales de calcio: Actúa como un abridor de canales de calcio, facilitando la entrada de calcio y mejorando la plasticidad sináptica
Análisis Bioquímico
Biochemical Properties
Nefiracetam interacts with various enzymes, proteins, and other biomolecules. It shows high affinity for the GABA A receptor, where it is presumed to be an agonist . It enhances both GABAergic and cholinergic signalling . It also exhibits antiamnesic effects against a number of memory impairing substances .
Cellular Effects
This compound has significant effects on various types of cells and cellular processes. It influences cell function by enhancing signalling of acetylcholine and glutamate at the synapse and then prolonging the calcium in the activated neuron . It also modulates the GABAA receptor-channel, playing a significant role in reducing neuronal excitability throughout the nervous system .
Molecular Mechanism
This compound exerts its effects at the molecular level through several mechanisms. It prolongs the opening of calcium channels, which enhances signalling of a receptor independent of the synapse . It also augments signalling through cholinergic receptors, which then releases most excitatory neurotransmitters from the presynaptic level .
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of this compound change over time. It does not appear to significantly affect memory formation acutely, but it can increase memory formation when taken daily over a prolonged period of time . It also shows a higher rate of neurogenesis with prolonged supplementation .
Dosage Effects in Animal Models
In animal models, the effects of this compound vary with different dosages. Animal studies using acute doses tend to note most benefits in the 3-10mg/kg range . This range has been repeatedly shown to enhance memory formation when taken daily over a prolonged period of time .
Metabolic Pathways
This compound is involved in various metabolic pathways. It is extensively metabolised, and its major metabolites in humans are 5-hydroxy-nefiracetam, 4-hydroxy-nefiracetam and N-[(2,6-dimethylphenylcarbamoyl)methyl]-succinamic acid .
Métodos De Preparación
Rutas sintéticas y condiciones de reacción: Nefiracetam se puede sintetizar a través de un proceso de varios pasos que involucra la reacción de 2,6-dimetilfenilamina con cloroacetato de etilo para formar un intermedio, que luego se cicla para producir this compound. Las condiciones de reacción generalmente implican el uso de solventes como etanol y catalizadores como etoxido de sodio .
Métodos de producción industrial: La producción industrial de this compound implica rutas sintéticas similares pero a mayor escala. El proceso se optimiza para obtener mayores rendimientos y pureza, a menudo involucrando pasos de purificación adicionales como recristalización y cromatografía para asegurar que el producto final cumpla con los estándares farmacéuticos .
Análisis De Reacciones Químicas
Tipos de reacciones: Nefiracetam experimenta varias reacciones químicas, incluyendo:
Oxidación: this compound se puede oxidar para formar derivados hidroxilados.
Reducción: Las reacciones de reducción pueden convertir this compound en su amina correspondiente.
Sustitución: this compound puede sufrir reacciones de sustitución nucleofílica, donde el grupo amina es reemplazado por otros nucleófilos.
Reactivos y condiciones comunes:
Oxidación: Los agentes oxidantes comunes incluyen permanganato de potasio y peróxido de hidrógeno.
Reducción: Se utilizan agentes reductores como hidruro de aluminio y litio y borohidruro de sodio.
Sustitución: Los nucleófilos como la azida de sodio y los tioles se emplean comúnmente.
Principales productos formados:
Oxidación: Derivados de this compound hidroxilados.
Reducción: Derivados de this compound aminados.
Sustitución: Varios compuestos de this compound sustituidos dependiendo del nucleófilo utilizado.
Comparación Con Compuestos Similares
Nefiracetam se compara con otras racetamas como:
Piracetam: La primera racetama, conocida por sus efectos de mejora cognitiva pero menos potente que el this compound.
Aniracetam: Similar al this compound pero con propiedades ansiolíticas adicionales.
Oxiracetam: Conocido por sus efectos estimulantes y mejora cognitiva.
Fenilpiracetam: Más potente que el piracetam, con propiedades estimulantes adicionales.
Pramiracetam: Altamente potente, utilizado principalmente para mejorar la memoria
This compound destaca por su combinación única de mejora cognitiva, neuroprotección y mejora del estado de ánimo, lo que lo convierte en un compuesto versátil en la familia de las racetamas.
Actividad Biológica
Nefiracetam, a pyrrolidone-type nootropic compound, has garnered attention for its potential cognitive-enhancing properties and various pharmacological effects. This article delves into the biological activity of this compound, highlighting its mechanisms of action, efficacy in clinical studies, and relevant case studies.
This compound exhibits multiple mechanisms that contribute to its biological activity:
- NMDA Receptor Modulation : this compound has been shown to potentiate the activity of N-methyl-D-aspartate (NMDA) receptors. It enhances NMDA currents through an allosteric mechanism, interacting with protein kinase C (PKC) pathways, which leads to increased phosphorylation and modulation of glycine binding sites on NMDA receptors. This effect is particularly significant as NMDA receptors play a crucial role in synaptic plasticity and memory formation .
- Cholinergic System Activation : The compound activates cholinergic pathways, which are essential for memory and learning. It has been observed to increase acetylcholine levels in the brain, thereby enhancing cognitive functions .
- Calcium Channel Activation : this compound activates L/N-type calcium channels, facilitating calcium influx that is critical for neurotransmitter release and neuronal excitability .
- Neuroprotective Effects : In models of retinal ischemia-reperfusion injury, this compound demonstrated significant neuroprotective actions, suggesting its potential utility in conditions involving oxidative stress and neuronal damage .
Case Studies and Clinical Trials
- Poststroke Apathy Study : A randomized, placebo-controlled trial evaluated the efficacy of this compound in treating apathy in stroke patients. Patients receiving 900 mg/day showed a decrease in apathy scores; however, the results did not reach statistical significance compared to placebo due to a small sample size (only 20 patients with apathy were randomized) . This highlights the need for larger multicenter studies to validate these findings.
- Cognitive Enhancement in Older Rabbits : Research conducted on older rabbits indicated that this compound significantly improved retention and relearning capabilities. The study found lasting effects on memory performance even after treatment cessation, suggesting a prolonged impact on cognitive functions .
- GABAergic Activity : In an animal model of cerebral ischemia, this compound was shown to restore GABA levels and enhance GABAergic activity, indicating its role in modulating inhibitory neurotransmission during ischemic events. This effect was more pronounced than its influence on cholinergic systems .
Summary of Findings
| Study Type | Sample Size | Dosage | Outcome |
|---|---|---|---|
| Poststroke Apathy | 20 | 900 mg/day | Decreased apathy scores; not statistically significant |
| Cognitive Enhancement (Rabbits) | 34 | 5-15 mg/kg | Improved retention and relearning capabilities |
| GABAergic Activity | Rat Model | 10 mg/kg | Restored GABA levels post-ischemia |
Propiedades
IUPAC Name |
N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C14H18N2O2/c1-10-5-3-6-11(2)14(10)15-12(17)9-16-8-4-7-13(16)18/h3,5-6H,4,7-9H2,1-2H3,(H,15,17) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
NGHTXZCKLWZPGK-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC1=C(C(=CC=C1)C)NC(=O)CN2CCCC2=O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C14H18N2O2 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID2020923 |
Source
|
| Record name | Nefiracetam | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID2020923 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
246.30 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
CAS No. |
77191-36-7 |
Source
|
| Record name | Nefiracetam | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=77191-36-7 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Nefiracetam [INN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0077191367 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Nefiracetam | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB13082 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Nefiracetam | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=759830 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | Nefiracetam | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID2020923 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/information-on-chemicals | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | NEFIRACETAM | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/1JK12GX30N | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
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Retrosynthesis Analysis
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