NEFIRACETAM

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

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 76 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 2678
GABA-A receptor; anion channel 202 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 2678
Protein kinase C alpha 20 Target ID: CHEMBL2855 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17095583	Activator 1430

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10820661	Primary	Phase III 656	Unknown Approved Use Unknown
Major depressive disorder 173 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 1132	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
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
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
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
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
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
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
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

AUC

Value	Dose	Analyte	Population
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
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
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
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
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
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

T_1/2

Value	Dose	Analyte	Population
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
4.78 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
3.77 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
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
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
3.85 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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 60	CYP1A2 1054 CYP2C19 991 P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144213342	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466286	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170466286	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466286	no

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11428655/	major [Km 5618 uM]
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11428655/	minor
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007185	no
CYP2C19 991	substrate 3367 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
Enamine	Z79686019	https://www.enaminestore.com/blog/real/?codes=Z79686019
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
MedChem Express	HY-B0340	https://www.medchemexpress.com/search.html?q=HY-B0340&ft=&fa=&fp=
MolPort	MolPort-006-666-274	https://www.molport.com/shop/molecule-link/MolPort-006-666-274
Molnova	M15918	https://www.molnova.com/en/serch-list.html?keywords=M15918
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
eMolecules	2728962	https://orderbb.emolecules.com/search/#?query=2728962
eNovation Chemicals	D491510	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D491510&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6030817685	https://mcule.com/MCULE-6030817685/
mcule	NGHTXZCKLWZPGK-UHFFFAOYSA-N	https://mcule.com/NGHTXZCKLWZPGK-UHFFFAOYSA-N/

PubMed

Title	Date	PubMed
Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice.	1990 Jun	2113296
Nefiracetam metabolism by human liver microsomes: role of cytochrome P450 3A4 and cytochrome P450 1A2 in 5-hydroxynefiracetam formation.	2001 Jun	11428655
Nefiracetam improves the impairment of local cerebral blood flow and glucose utilization after chronic focal cerebral ischemia in rats.	2002	11834887
Nefiracetam ameliorates associative learning impairment in the scopolamine-injected older rabbit.	2002 Apr	11951055
Nefiracetam. Daiichi Seiyaku.	2002 May	12090554
Effects of nefiracetam on spatial memory function and acetylcholine and GABA metabolism in microsphere-embolized rats.	2002 Oct 18	12393060
Effects of nefiracetam on cerebral adenylyl cyclase activity in rats with microsphere embolism-induced memory dysfunction.	2003 Mar	12612440
Negative regulation of opioid receptor-G protein-Ca2+ channel pathway by the nootropic nefiracetam.	2004 Oct	15542741
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 Jan 10	15659294
Modulation of N-methyl-D-aspartate receptors by donepezil in rat cortical neurons.	2005 Oct	15951396
Anticonvulsant and neuroprotective effects of the novel nootropic agent nefiracetam on kainic acid-induced seizures in rats.	2005 Sep 28	16122714
Nefiracetam potentiates N-methyl-D-aspartate (NMDA) receptor function via protein kinase C activation and reduces magnesium block of NMDA receptor.	2007 Feb	17095583
Double-blind randomized treatment of poststroke depression using nefiracetam.	2008 Spring	18451188
Essential role of neuron-enriched diacylglycerol kinase (DGK), DGKbeta in neurite spine formation, contributing to cognitive function.	2010 Jul 15	20657643
Synthesis of N-substituted Clausenamide analogues.	2010 Nov	20864223

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%.

Name

Type

Language

NEFIRACETAM

Official Name

English

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

Common Name

English

NSC-759830

Code

English

nefiracetam [INN]

Common Name

English

NEFIRACETAM [MI]

Common Name

English

NEFIRACETAM [MART.]

Common Name

English

NEFIRACETAM [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1509