Chemistry:Nefiracetam

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Short description: Chemical compound
Nefiracetam
Nefiracetam.svg
Nefiracetam3d.png
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: Unscheduled
Pharmacokinetic data
Elimination half-life3-5 hours[1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC14H18N2O2
Molar mass246.310 g·mol−1
3D model (JSmol)
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Nefiracetam is a nootropic drug of the racetam family. Preliminary research suggests that it may possess certain antidementia properties in rats.[2]

Effects

Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, and monoaminergic neuronal systems.[citation needed] 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.[3][4] In addition, research in animal models suggests antiamnesic effects against a number of memory impairing substances, including: ethanol, chlorodiazepoxide, scopolamine, bicuculline, picrotoxin, and cycloheximide.[5]

Pharmacology

Unlike other racetams, nefiracetam shows high affinity for the GABAA receptor (IC50) = 8.5 nM), where it is presumed to be an agonist.[6][7] It was able to potently inhibit 80% of muscimol binding to the GABAA receptor, although it failed to displace the remaining 20% of specific muscimol binding.[6][7] Nefiracetam is able to reverse the amnesia caused by the GABAA receptor antagonists picrotoxin and bicuculline in mice, although it failed to prevent seizures induced by these drugs.[7]

Concerns

Studies of long-term consumption of nefiracetam in humans and primates have shown it to have no toxicity.[8][9] However, animals which metabolize nefiracetam differently from humans and primates are at risk for renal and testicular[10][11] toxicity. Dogs especially are particularly sensitive, which has been shown to be caused by a specific metabolite, M-18.[12] 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.[8][9]

See also

References

  1. ↑ "Single- and multiple-dose pharmacokinetics of nefiracetam, a new nootropic agent, in healthy volunteers". The Journal of Pharmacy and Pharmacology 44 (9): 750–754. September 1992. doi:10.1111/j.2042-7158.1992.tb05513.x. PMID 1360528. 
  2. ↑ "Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing". Neuropsychopharmacology 31 (1): 90–100. January 2006. doi:10.1038/sj.npp.1300810. PMID 15988469. 
  3. ↑ "Double-blind treatment of apathy in patients with poststroke depression using nefiracetam". The Journal of Neuropsychiatry and Clinical Neurosciences 21 (2): 144–151. 2009. doi:10.1176/appi.neuropsych.21.2.144. PMID 19622685. 
  4. ↑ "Double-blind randomized treatment of poststroke depression using nefiracetam". The Journal of Neuropsychiatry and Clinical Neurosciences 20 (2): 178–184. 2008. doi:10.1176/appi.neuropsych.20.2.178. PMID 18451188. 
  5. ↑ "Effects of nefiracetam on amnesia animal models with neuronal dysfunctions". Behavioural Brain Research 83 (1–2): 107–115. February 1997. doi:10.1016/s0166-4328(97)86053-6. PMID 9062668. 
  6. ↑ 6.0 6.1 "Piracetam and other structurally related nootropics". Brain Research. Brain Research Reviews 19 (2): 180–222. May 1994. doi:10.1016/0165-0173(94)90011-6. PMID 8061686. 
  7. ↑ 7.0 7.1 7.2 "Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions". European Journal of Pharmacology 178 (2): 143–149. March 1990. doi:10.1016/0014-2999(90)90469-m. PMID 2328758. 
  8. ↑ 8.0 8.1 "Phase I study on DM-9384 (nefiracetam)". Jpn. Pharmacol. Ther. 22: 3539–3587. 1994. 
  9. ↑ 9.0 9.1 "Clinical evaluation of DM-9384 in the treatment of cerebrovascular disorders: early phase II study". Jpn. Pharmacol. Ther. (22): 3589–3624. 1994. 
  10. ↑ "Investigation of testicular toxicity of nefiracetam, a neurotransmission enhancer, in rats". Toxicology Letters 143 (3): 307–315. August 2003. doi:10.1016/s0378-4274(03)00197-8. PMID 12849691. 
  11. ↑ "Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer". Reproductive Toxicology 18 (3): 423–430. May 2004. doi:10.1016/j.reprotox.2004.01.008. PMID 15082078. 
  12. ↑ "Effect of nefiracetam, a neurotransmission enhancer, on primary uroepithelial cells of the canine urinary bladder". Toxicological Sciences 72 (1): 164–170. March 2003. doi:10.1093/toxsci/kfg010. PMID 12604846. 

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See also
Receptor/signaling modulators
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