Nefiracetam

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.{{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 }}{{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 }} In addition, research in animal models suggests antiamnesic effects against a number of memory impairing substances, including: ethanol, chlorodiazepoxide, scopolamine, bicuculline, picrotoxin, and cycloheximide.{{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 }}

Unlike other racetams, nefiracetam shows high affinity for the GABA_A receptor (IC₅₀) = 8.5 nM), where it is presumed to be an agonist.{{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 }}{{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 }} It was able to potently inhibit 80% of muscimol binding to the GABA_A receptor, although it failed to displace the remaining 20% of specific muscimol binding. Nefiracetam is able to reverse the amnesia caused by the GABA_A receptor antagonists picrotoxin and bicuculline in mice, although it failed to prevent seizures induced by these drugs.

Studies of long-term consumption of nefiracetam in humans and primates have shown it to have no toxicity.{{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}}{{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 }} However, animals which metabolize nefiracetam differently from humans and primates are at risk for renal and testicular{{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 }}{{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 }} 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.{{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 }} 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.

• Racetams
• Guvacine
• Phenibut

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{{Racetams}}

{{GABAA receptor modulators}}

Category:Racetams

Category:Acetanilides

Category:GABAA receptor agonists