CX614

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Chemical compound

title: "CX614" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["pyrrolidines", "ampakines", "lactams", "benzodioxoles", "ampa-receptor-positive-allosteric-modulators", "experimental-drugs"] description: "Chemical compound" topic_path: "general/pyrrolidines" source: "https://en.wikipedia.org/wiki/CX614" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

| verifiedrevid = 455090650 | IUPAC_name = 2H,3H,6aH-pyrrolidino(2*,1*-3',2')1,3-oxazino(6',5'-5,4)benzo(e)1,4-dioxan-10-one | image = CX614.png | image_class = skin-invert-image | alt = Skeletal formula | width = 200 | image2 = CX614 molecule ball.png | image_class2 = bg-transparent | alt2 = Ball-and-stick model of CX614 | width2 = 215

| tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = Investigational New Drug | legal_status = | routes_of_administration =

| bioavailability = | protein_bound = | metabolism = | excretion =

| IUPHAR_ligand = 7842 | CAS_number_Ref = | CAS_number = 191744-13-5 | ATC_prefix = | ATC_suffix = | PubChem = 6451148 | DrugBank_Ref = | DrugBank = | UNII_Ref = | UNII = 87V631480W | ChemSpiderID = 4953628 | C=13 | H=13 | N=1 | O=4 | smiles = C1CC2N(C1)C(=O)C3=CC4=C(C=C3O2)OCCO4 | StdInChI = 1S/C13H13NO4/c15-13-8-6-10-11(17-5-4-16-10)7-9(8)18-12-2-1-3-14(12)13/h6-7,12H,1-5H2 | StdInChIKey = RQEPVMAYUINZRE-UHFFFAOYSA-N | synonyms = CX-614

CX-614 is an ampakine drug developed by Cortex Pharmaceuticals. It has been investigated for its effect on AMPA receptors.

Chronic CX-614 treatments produce rapid increases in the synthesis of the brain-derived neurotrophic factor BDNF which has very important effects on synaptic plasticity and may have applications in the treatment of neurodegenerative diseases such as Alzheimer's disease.

Acute CX-614 treatments activate local mRNA translation (new protein synthesis) within dendrites and this is mediated by a fast upregulation of BDNF release. CX-614-dependent release of BDNF rapidly increases translation of proteins that are important for synaptic plasticity such as ARC/Arg3.1 and CaMKIIalpha.

CX-614 has also been proposed as a treatment for conditions such as depression and schizophrenia, but produces receptor downregulation following chronic administration, which might limit the potential for extended use.

However, downregulation of AMPA receptors with prolonged CX-614 administration can be avoided by designing and using short and intermittent treatment protocols, which could still upregulate BDNF protein levels without reducing the levels of AMPA receptors.

Importantly, such short and intermittent treatment protocols are neuroprotective against neurotoxicity induced with MPTP and MPP+ in cultured midbrain (mesencephalic) and hippocampal organotypic slices.

These results uncovered the neuroprotective effects of CX-614 and indicated that opened the way for further experimentation with CX-614 as an important new treatment for Parkinson's disease and Alzheimer's disease.

CX-614 has also been shown to reduce the behavioural effects of methamphetamine in mice, and may have application in the treatment of stimulant abuse.

References

References

  1. (2000). "Effects of the potent ampakine CX614 on hippocampal and recombinant AMPA receptors: interactions with cyclothiazide and GYKI 52466". Mol. Pharmacol..
  2. (Oct 2003). "Chronic elevation of brain-derived neurotrophic factor by ampakines". J Pharmacol Exp Ther.
  3. (Jul 2009). "POSITIVE AMPA RECEPTOR MODULATION RAPIDLY STIMULATES BDNF RELEASE AND INCREASES DENDRITIC mRNA TRANSLATION". J. Neurosci..
  4. (Sep 2005). "Mechanism of positive allosteric modulators acting on AMPA receptors". J. Neurosci..
  5. Lynch G. (Feb 2006). "Glutamate-based therapeutic approaches: ampakines". Curr Opin Pharmacol.
  6. (Jul 2005). "Prolonged Positive Modulation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Induces Calpain-Mediated PSD-95/Dlg/ZO-1 Protein Degradation and AMPA Receptor Down-Regulation in Cultured Hippocampal Slices". J Pharmacol Exp Ther.
  7. (Apr 2007). "Targeting AMPA Receptor Gating Processes with Allosteric Modulators and Mutations". Biophys. J..
  8. (Mar 2009). "Ampakines cause sustained increases in BDNF signaling at excitatory synapses without changes in AMPA receptor subunit expression". Neuroscience.
  9. (Apr 2009). "BDNF mediates the neuroprotective effects of positive AMPA receptor modulators against MPP+-induced toxicity in cultured hippocampal and mesencephalic slices". Neuropharmacology.
  10. (2003). "Ampakines reduce methamphetamine-driven rotation and activate neocortex in a regionally selective fashion". Neuroscience.

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pyrrolidinesampakineslactamsbenzodioxolesampa-receptor-positive-allosteric-modulatorsexperimental-drugs