{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 458287215 | IUPAC_name = ''N''-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide | image = Nefiracetam.svg | image_class = skin-invert-image | width = 150px | image2 = Nefiracetam3d.png | image_class2 = bg-transparent

<!--Clinical data--> | tradename = | pregnancy_category = | legal_AU = S4 | legal_US = Unscheduled | routes_of_administration = Oral

<!--Pharmacokinetic data--> | bioavailability = | metabolism = | excretion = | elimination_half-life = 3-5 hours<ref>{{cite journal | vauthors = Fujimaki Y, Sudo K, Hakusui H, Tachizawa H, Murasaki M | title = Single- and multiple-dose pharmacokinetics of nefiracetam, a new nootropic agent, in healthy volunteers | journal = The Journal of Pharmacy and Pharmacology | volume = 44 | issue = 9 | pages = 750–754 | date = September 1992 | pmid = 1360528 | doi = 10.1111/j.2042-7158.1992.tb05513.x | s2cid = 25913554 }}</ref>

<!--Identifiers--> | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 77191-36-7 | ATC_prefix = none | PubChem = 71157 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 64299 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 1JK12GX30N | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 260829

<!--Chemical data--> | C=14 | H=18 | N=2 | O=2 | SMILES = O=C2N(CC(=O)Nc1c(cccc1C)C)CCC2 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = NGHTXZCKLWZPGK-UHFFFAOYSA-N }}

'''Nefiracetam''' is a nootropic drug of the racetam family. Preliminary research suggests that it may possess certain antidementia properties in rats.<ref name=NPP2005>{{cite journal | vauthors = Murphy KJ, Foley AG, O'connell AW, Regan CM | title = Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing | journal = Neuropsychopharmacology | volume = 31 | issue = 1 | pages = 90–100 | date = January 2006 | pmid = 15988469 | doi = 10.1038/sj.npp.1300810 | doi-access = free }}</ref>

==Effects== Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, and monoaminergic neuronal systems.{{Citation needed|date=July 2018}} Preliminary studies suggest that it improves apathy and motivation in post-stroke patients. It may also exhibit antiamnesia effects for the Alzheimer's type and cerebrovascular type of dementia.<ref>{{cite journal | vauthors = Robinson RG, Jorge RE, Clarence-Smith K, Starkstein S | title = Double-blind treatment of apathy in patients with poststroke depression using nefiracetam | journal = The Journal of Neuropsychiatry and Clinical Neurosciences | volume = 21 | issue = 2 | pages = 144–151 | year = 2009 | pmid = 19622685 | doi = 10.1176/appi.neuropsych.21.2.144 }}</ref><ref>{{cite journal | vauthors = Robinson RG, Jorge RE, Clarence-Smith K | title = Double-blind randomized treatment of poststroke depression using nefiracetam | journal = The Journal of Neuropsychiatry and Clinical Neurosciences | volume = 20 | issue = 2 | pages = 178–184 | year = 2008 | pmid = 18451188 | doi = 10.1176/appi.neuropsych.20.2.178 }}</ref> In addition, research in animal models suggests antiamnesic effects against a number of memory impairing substances, including: ethanol, chlorodiazepoxide, scopolamine, bicuculline, picrotoxin, and cycloheximide.<ref name="Effects of nefiracetam on amnesia animal models with neuronal dysfunctions">{{cite journal | vauthors = Hiramatsu M, Shiotani T, Kameyama T, Nabeshima T | title = Effects of nefiracetam on amnesia animal models with neuronal dysfunctions | journal = Behavioural Brain Research | volume = 83 | issue = 1–2 | pages = 107–115 | date = February 1997 | pmid = 9062668 | doi = 10.1016/s0166-4328(97)86053-6 | s2cid = 4045550 }}</ref>

==Pharmacology== Unlike other racetams, nefiracetam shows high affinity for the GABA<sub>A</sub> receptor (IC<sub>50</sub> = 8.5&nbsp;nM), where it is presumed to be an agonist.<ref name="pmid8061686">{{cite journal | vauthors = Gouliaev AH, Senning A | title = Piracetam and other structurally related nootropics | journal = Brain Research. Brain Research Reviews | volume = 19 | issue = 2 | pages = 180–222 | date = May 1994 | pmid = 8061686 | doi = 10.1016/0165-0173(94)90011-6 | s2cid = 18122566 }}</ref><ref name="pmid2328758">{{cite journal | vauthors = Nabeshima T, Noda Y, Tohyama K, Itoh J, Kameyama T | title = Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions | journal = European Journal of Pharmacology | volume = 178 | issue = 2 | pages = 143–149 | date = March 1990 | pmid = 2328758 | doi = 10.1016/0014-2999(90)90469-m }}</ref> It was able to potently inhibit 80% of muscimol binding to the GABA<sub>A</sub> receptor, although it failed to displace the remaining 20% of specific muscimol binding.<ref name="pmid8061686" /><ref name="pmid2328758" /> Nefiracetam is able to reverse the amnesia caused by the GABA<sub>A</sub> receptor antagonists picrotoxin and bicuculline in mice, although it failed to prevent seizures induced by these drugs.<ref name="pmid2328758" />

==Concerns== Studies of long-term consumption of nefiracetam in humans and primates have shown it to have no toxicity.<ref name="Murasaki_1994">{{cite journal| vauthors = Murasaki M, Inami M, Ishigooka J, Watanabe H, Utsumi M, Matsumoto T |title=Phase I study on DM-9384 (nefiracetam)|journal=Jpn. Pharmacol. Ther.|year=1994|volume=22|pages=3539–3587|display-authors=etal}}</ref><ref name="Otomo_1994_2">{{cite journal| vauthors = Otomo E, Kogure K, Hirai S, Goto F, Hasegawa K, Tazaki Y, etal |title=Clinical evaluation of DM-9384 in the treatment of cerebrovascular disorders: early phase II study|journal=Jpn. Pharmacol. Ther.|year=1994|issue=22|pages=3589–3624 }}</ref> However, animals which metabolize nefiracetam differently from humans and primates are at risk for renal and testicular<ref>{{cite journal | vauthors = Shimada M, Shikanai Y, Shimomura K, Harada S, Watanabe G, Taya K, Kato M, Furuhama K | display-authors = 6 | title = Investigation of testicular toxicity of nefiracetam, a neurotransmission enhancer, in rats | journal = Toxicology Letters | volume = 143 | issue = 3 | pages = 307–315 | date = August 2003 | pmid = 12849691 | doi = 10.1016/s0378-4274(03)00197-8 }}</ref><ref name=Shimomura>{{cite journal | vauthors = Shimomura K, Shimada M, Hagiwara M, Harada S, Kato M, Furuhama K | title = Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer | journal = Reproductive Toxicology | volume = 18 | issue = 3 | pages = 423–430 | date = May 2004 | pmid = 15082078 | doi = 10.1016/j.reprotox.2004.01.008 }}</ref> toxicity. Dogs especially are particularly sensitive, which has been shown to be caused by a specific metabolite, M-18 which isn't formed in humans.<ref name="Goto">{{cite journal | vauthors = Goto K, Ishii Y, Jindo T, Furuhama K | title = Effect of nefiracetam, a neurotransmission enhancer, on primary uroepithelial cells of the canine urinary bladder | journal = Toxicological Sciences | volume = 72 | issue = 1 | pages = 164–170 | date = March 2003 | pmid = 12604846 | doi = 10.1093/toxsci/kfg010 | doi-access = free }}</ref> Higher doses than those in dogs were needed to cause testicular toxicity in rats, although no toxicity was seen in monkeys. Additionally, there has been no evidence of toxicity during clinical trials.<ref name="Murasaki_1994"/><ref name="Otomo_1994_2"/>

== See also == *Racetams *Guvacine *Phenibut

== References == {{Reflist}}

{{Racetams}} {{GABAA receptor modulators}}

Category:Racetams Category:Acetanilides Category:GABAA receptor agonists