NEFIRACETAM

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H18N2O2
Molecular Weight	246.3049
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=CC(C)=C1NC(=O)CN2CCCC2=O

InChI

InChIKey=NGHTXZCKLWZPGK-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C14H18N2O2
Molecular Weight	246.3049
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.smarternootropics.com/nefiracetam/
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/10820661 | http://adisinsight.springer.com/drugs/800001382

Nefiracetam is a cyclic derivative of gamma-aminobutyric acid (GABA). It is thought to act by normalising dysfunctional acetylcholine, GABA and possibly monoamine neurotransmitter systems, but it may also facilitate N/L-type calcium channel opening. Nefiracetam has received attention as a treatment for seizures, depression, and dementia. Nefiracetam was found to be extremely testicular toxic in both rats and dogs; it was found to significantly decrease the levels of testicular testosterone leading to atrophy and malformation of sperm.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neuronal acetylcholine receptor; alpha4/beta2 77 Target ID: CHEMBL1907596 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19272425 \| http://www.smarternootropics.com/nefiracetam/ \| http://adisinsight.springer.com/drugs/800001382 \| https://www.ncbi.nlm.nih.gov/pubmed/15516710	Agonist 2752
GABA-A receptor; anion channel 203 Target ID: CHEMBL1907607 Sources: http://adisinsight.springer.com/drugs/800001382 \| https://www.ncbi.nlm.nih.gov/pubmed/9014140 \| https://www.ncbi.nlm.nih.gov/pubmed/2328758	Agonist 2752
Protein kinase C alpha 21 Target ID: CHEMBL2855 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17095583	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 278 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10820661	Primary	Phase III 665	Unknown Approved Use Unknown
Major depressive disorder 179 Sources: http://www.smarternootropics.com/nefiracetam/ https://www.ncbi.nlm.nih.gov/pubmed/19622685 https://www.ncbi.nlm.nih.gov/pubmed/18451188	Primary	Phase II 1147	Unknown Approved Use Unknown
Epilepsy 121 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10771248 https://www.ncbi.nlm.nih.gov/pubmed/23603142 https://www.ncbi.nlm.nih.gov/pubmed/16190926 https://www.ncbi.nlm.nih.gov/pubmed/16122714	Primary	Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
10.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
22.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2.08 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.02 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.97 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
0.68 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	200 mg 3 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
16.3 μM REVIEW https://www.ncbi.nlm.nih.gov/pubmed/10820661	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
78.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
167 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
16.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
27.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
19.59 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
5.67 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
3.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3.77 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4.78 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.33 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
5.86 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4.43 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1360528	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3.9 h REVIEW https://www.ncbi.nlm.nih.gov/pubmed/10820661	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	NEFIRACETAM serum	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 429	CYP1A2 1197 CYP2C19 1119 P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144213342	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466286	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170466286	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466286	no

Drug as victim

Target	Modality	Activity
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11428655/	major [Km 5618 uM]
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11428655/	minor
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007185	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11428655/	yes [Km 442 uM]

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P008O32	https://www.1pchem.com/search?query=1P008O32
A2B Chem	AE03662	http://a2bchem.com/prod/AE03662
AK Scientific	I625	https://aksci.com/item_detail.php?cat=I625
Angene	AGN-PC-0WH9OQ	http://www.angenechemical.com/productshow/AGN-PC-0WH9OQ.html
ApexBio Technology	B1532	https://www.apexbt.com/catalogsearch/result/?q=B1532
AsisChem	I76062	https://asischem.com/catalogsearch/result/?q=I76062
AstaTech	T72927	http://astatechinc.com/CPSResult.php?CRNO=T72927
BOC Sciences	77191-36-7	http://www.bocsci.com/description.asp?cas=77191-36-7
Chem Scene	CS-2382	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2382
ChemShuttle	113634	https://www.chemshuttle.com/catalogsearch/result/?q=113634
eMolecules	2728962	https://orderbb.emolecules.com/search/#?query=2728962
Enamine	Z79686019	https://www.enaminestore.com/blog/real/?codes=Z79686019
eNovation Chemicals	D491510	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D491510&searchbtn.x=0&searchbtn.y=0
Fluorochem	241232	http://www.fluorochem.co.uk/Products/Product?code=241232
Hairui	HR135906	http://www.hairuichem.com/en/product/search.do?q=HR135906
KeyOrganics	KS-5226	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=KS-5226
Lab Network	LN01342301	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342301
Lab Seeker	SC-25780	http://www.labseeker.com/search.php?keywords=SC-25780&category=0
LabSeeker	SC-25780	http://www.labseeker.com/search.php?keywords=SC-25780&category=0
Matrix Scientific	147751	http://www.matrixscientific.com/147751.html
mcule	MCULE-6030817685	https://mcule.com/MCULE-6030817685/
mcule	NGHTXZCKLWZPGK-UHFFFAOYSA-N	https://mcule.com/NGHTXZCKLWZPGK-UHFFFAOYSA-N/
MedChem Express	HY-B0340	https://www.medchemexpress.com/search.html?q=HY-B0340&ft=&fa=&fp=
Molnova	M15918	https://www.molnova.com/en/serch-list.html?keywords=M15918
MolPort	MolPort-006-666-274	https://www.molport.com/shop/molecule-link/MolPort-006-666-274
MuseChem	I007701	https://www.musechem.com/product/I007701.html
Otava	4473996	https://search.otavachemicals.com/#!/search?query=4473996&type=code
PI Chemicals	PI-21860	http://www.pipharm.com/catalog_products/PI-21860.html
Ryan Scientific	Mechlorethamine_HCl	https://ryansci.com/products?q=Mechlorethamine_HCl&list_q=&search_type=exact
Selleck Chemicals	S1969	http://www.selleckchem.com/search.html?searchDTO.searchParam=S1969
TargetMol	T0169	https://www.targetmol.com/search?keyword=T0169
Tetrahedron	TS62322	http://www.thsci.com/search.do?q=TS62322
TimTec	ST102877	http://www.echemstore.com/catalogsearch/result/?q=ST102877
Tocris	2851	https://www.tocris.com/search.php?Type=QuickSearch&Value=2851
W&J PharmaChem	50C512359	http://wjpharmachem.com/new/searcht.php?keyword=50C512359

PubMed

Title	Date	PubMed
E22Δ Mutation in Amyloid β-Protein Promotes β-Sheet Transformation, Radical Production, and Synaptotoxicity, But Not Neurotoxicity.	2010-12-19	21234376
Synthesis of N-substituted Clausenamide analogues.	2010-11	20864223
Essential role of neuron-enriched diacylglycerol kinase (DGK), DGKbeta in neurite spine formation, contributing to cognitive function.	2010-07-15	20657643
Apathy following stroke.	2010-06	20540829
Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.	2010-02-12	20166767
Trace eyeblink conditioning is impaired in α7 but not in β2 nicotinic acetylcholine receptor knockout mice.	2010	20976039
Nefiracetam activation of CaM kinase II and protein kinase C mediated by NMDA and metabotropic glutamate receptors in olfactory bulbectomized mice.	2009-07	19457128
Nefiracetam and galantamine modulation of excitatory and inhibitory synaptic transmission via stimulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons.	2009-05-05	19272425
Improvement of depressive behaviors by nefiracetam is associated with activation of CaM kinases in olfactory bulbectomized mice.	2009-04-10	19233146
Double-blind treatment of apathy in patients with poststroke depression using nefiracetam.	2009	19622685
CaM kinase II and protein kinase C activations mediate enhancement of long-term potentiation by nefiracetam in the rat hippocampal CA1 region.	2008-08	18445137
Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity.	2008-03-01	18312687
Double-blind randomized treatment of poststroke depression using nefiracetam.	2008	18451188
Nefiracetam potentiates N-methyl-D-aspartate (NMDA) receptor function via protein kinase C activation and reduces magnesium block of NMDA receptor.	2007-02	17095583
Discriminative-stimulus effects of methamphetamine and morphine in rats are attenuated by cAMP-related compounds.	2006-10-02	16857277
Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing.	2006-01	15988469
Effects of Nefiracetam, a novel pyrrolidone-type nootropic agent, on the amygdala-kindled seizures in rats.	2005-10	16190926
Modulation of N-methyl-D-aspartate receptors by donepezil in rat cortical neurons.	2005-10	15951396
Anticonvulsant and neuroprotective effects of the novel nootropic agent nefiracetam on kainic acid-induced seizures in rats.	2005-09-28	16122714
Investigation on urinary proteins and renal mRNA expression in canine renal papillary necrosis induced by nefiracetam.	2005-09	16007418
[Evaluation methods for the discriminative stimulus and possible mechanisms of discriminative stimulus effects of methamphetamine in the rat].	2005-07	16141613
Pre-injury administration of morphine prevents development of neuropathic hyperalgesia through activation of descending monoaminergic mechanisms in the spinal cord in mice.	2005-06-03	15932652
Anticonvulsant properties of the novel nootropic agent nefiracetam in seizure models of mice and rats.	2005-06	15946322
Effects of nefiracetam on the levels of brain-derived neurotrophic factor and synapsin I mRNA and protein in the hippocampus of microsphere-embolized rats.	2005-01-10	15659294
Early pathophysiological features in canine renal papillary necrosis induced by nefiracetam.	2005	16105799
Mechanisms of action of cognitive enhancers on neuroreceptors.	2004-11	15516710
Negative regulation of opioid receptor-G protein-Ca2+ channel pathway by the nootropic nefiracetam.	2004-10	15542741
Nefiracetam attenuates methamphetamine-induced discriminative stimulus effects in rats.	2004-10	15542727
Nootropic nefiracetam inhibits proconvulsant action of peripheral-type benzodiazepines in epileptic mutant EL mice.	2004-10	15542710
Nefiracetam and physostigmine: separate and combined effects on learning in older rabbits.	2004-07	15165705
Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer.	2004-05	15082078
The cognition-enhancer nefiracetam inhibits both necrosis and apoptosis in retinal ischemic models in vitro and in vivo.	2004-04	14718588
Unique mechanism of action of Alzheimer's drugs on brain nicotinic acetylcholine receptors and NMDA receptors.	2003-12-05	14607256
Potentiation of N-methyl-D-aspartate-induced currents by the nootropic drug nefiracetam in rat cortical neurons.	2003-10	12805478
Investigation of testicular toxicity of nefiracetam, a neurotransmission enhancer, in rats.	2003-08-28	12849691
Comprehensive evaluation of canine renal papillary necrosis induced by nefiracetam, a neurotransmission enhancer.	2003-08-15	12954368
Effects of nefiracetam on cerebral adenylyl cyclase activity in rats with microsphere embolism-induced memory dysfunction.	2003-03	12612440
Effect of nefiracetam, a neurotransmission enhancer, on primary uroepithelial cells of the canine urinary bladder.	2003-03	12604846
A possible mechanism for improvement by a cognition-enhancer nefiracetam of spatial memory function and cAMP-mediated signal transduction system in sustained cerebral ischaemia in rats.	2003-02	12598418
Persistent effects of delayed treatment with nefiracetam on the water maze task in rats with sustained cerebral ischemia.	2003-02	12538802
Nefiracetam induces a long-lasting facilitation of hippocampal postsynaptic responses in mice lacking the NMDA receptor epsilon1 subunit.	2002-11-22	12426061
Effects of nefiracetam on spatial memory function and acetylcholine and GABA metabolism in microsphere-embolized rats.	2002-10-18	12393060
The long-term effects of nefiracetam on learning in older rabbits.	2002-10-17	12385816
No spatial working memory deficit in beta-amyloid-exposed rats. A longitudinal study.	2002-06	12369272
Basic science and epilepsy: experimental epilepsy surgery.	2001	12378083
Quantitative effects of nefiracetam on spatial learning of rats after cerebral embolism.	2000-09-10	17903808
Nefiracetam prevents propofol-induced anterograde and retrograde amnesia in the rodent without compromising quality of anesthesia.	1998-09	9743408
Nefiracetam (DM-9384) reverses apomorphine-induced amnesia of a passive avoidance response: delayed emergence of the memory retention effects.	1996-06	8829135
Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice.	1990-06	2113296
Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384) on learning and memory in rats.	1989-05	2724699

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage lies between 8.721mg/kg and 29.072mg/kg in humans for treating the negative cognitive effects of seizures as well as treating severely depressed individuals

Route of Administration: Oral

In Vitro Use Guide

The effects of nefiracetam on GABA-induced chloride currents were studied with rat dorsal root ganglion neurons in primary culture using the whole-cell patch-clamp technique. The dose-response curve for GABA-induced currents was shifted by 16 uM to lower concentrations by 10 uM nefiracetam while the maximal response was reduced by 22.84 +/- 0.68%.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:00:37 GMT 2025` Edited by `admin` on `Mon Mar 31 18:00:37 GMT 2025`
Record UNII	1JK12GX30N
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

NEFIRACETAM

Official Name

English

NEFIRACETAM [MI]

Preferred Name

English

2-OXO-1-PYRROLIDINEACETO-2',6'-XYLIDIDE

Common Name

English

NSC-759830

Code

English

nefiracetam [INN]

Common Name

English

NEFIRACETAM [MART.]

Common Name

English

NEFIRACETAM [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1509