Licostinel

Chemical compound

None

Identifiers

IUPAC name

6,7-Dichloro-5-nitro-1,4-dihydro-2,3-quinoxalinedione

CAS Number

153504-81-5

PubChem CID

5486198

ChemSpider

4588899

UNII

3Z3037LJTC

CompTox Dashboard (EPA)

DTXSID60165346

Chemical and physical dataFormulaC₈H₃Cl₂N₃O₄Molar mass276.03 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

c1c2c(c(c(c1Cl)Cl)[N+](=O)[O-])[nH]c(=O)c(=O)[nH]2

InChI

InChI=1S/C8H3Cl2N3O4/c9-2-1-3-5(6(4(2)10)13(16)17)12-8(15)7(14)11-3/h1H,(H,11,14)(H,12,15)
Key:CHFSOFHQIZKQCR-UHFFFAOYSA-N

Licostinel (INN) (code name ACEA-1021) is a competitive, silent antagonist of the glycine site of the NMDA receptor (K_b = 5 nM).^[1]^[2]^[3] It was under investigation by Acea Pharmaceuticals as a neuroprotective agent for the treatment of cerebral ischemia associated with stroke and head injuries but was ultimately never marketed.^[1]^[2]^[4] In clinical trials, licostinel did not produce phencyclidine-like psychotomimetic effects at the doses tested, though transient sedation, dizziness, and nausea were observed.^[4]^[5] In addition to its actions at the NMDA receptor, licostinel also acts as an antagonist of the AMPA and kainate receptors at high concentrations (K_b = 0.9 μM and 2.5 μM, respectively).^[3]

References

^ ^a ^b Small DL, Tauskela JS (31 January 2007). "Glutamate Receptor Pharmacology: Lessons Learned from the Last Decade of Stroke Trials". In Gill S, Pulido O (eds.). Glutamate Receptors in Peripheral Tissue: Excitatory Transmission Outside the CNS. Springer Science & Business Media. pp. 36–. ISBN 978-0-306-48644-9.
^ ^a ^b Gusev EI, Skvortsova VI (30 April 2003). "Primary Neuroprotection". Brain Ischemia. Springer Science & Business Media. pp. 249–. ISBN 978-0-306-47694-5.
^ ^a ^b Wilding TJ, Huettner JE (March 1996). "Antagonist pharmacology of kainate- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-preferring receptors". Molecular Pharmacology. 49 (3): 540–546. PMID 8643094.
^ ^a ^b Boyce SG, Rupniak N (1 January 2002). "Behavioural studies on the potential of NMDA receptor antagonists as analgesics". In Sirinathsinghji DJ, Hill RG (eds.). NMDA Antagonists As Potential Analgesic Drugs. Springer Science & Business Media. pp. 151–. ISBN 978-3-7643-6011-5.
^ Chizh BA, Headly PM (28 May 2013). "N-Methyl-D-Aspartate (NMDA) Receptors as Target for Pain Therapy". In Bountra C, Munglani R, Schmidt WK (eds.). Pain: Current Understanding, Emerging Therapies, and Novel Approaches to Drug Discovery. CRC Press. pp. 567–. ISBN 978-0-203-91125-9.