Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug;57(8):3498-3507.
doi: 10.1007/s12035-020-01954-x. Epub 2020 Jun 13.

Antidepressant-Like Effects of CX717, a Positive Allosteric Modulator of AMPA Receptors

Marta Gordillo-Salas  1 , Raquel Pascual-Antón  1 , Jun Ren  2 , John Greer  2 , Albert Adell  3   4
Affiliations

Antidepressant-Like Effects of CX717, a Positive Allosteric Modulator of AMPA Receptors

Marta Gordillo-Salas et al. Mol Neurobiol. 2020 Aug.

Abstract

Conventional antidepressant drugs elevate the availability of monoamine neurotransmitters. However, these pharmacological therapies have limited efficacy and a slow onset of action as main limitations. New glutamatergic drugs such as ketamine have shown promise as a rapid-acting antidepressant drugs although with adverse effects. The mechanism of action of ketamine is hypothesized to involve a dis-inhibition of cortical pyramidal neurons produced by an stimulation of AMPA receptors by glutamate. In this context, low-impact positive allosteric modulators of the AMPA receptors (a.k.a. ampakines) have been regarded as potential antidepressant drugs. Here, we have examined the behavioral, biochemical, and molecular effects of a low-impact ampakine, CX717. Our results show that CX717 has a rapid (30 min) but short-lasting (up to 24 h) antidepressant-like effect in the forced swim test. Intra-cortical infusion of CX717 increases the efflux of noradrenaline, dopamine, and serotonin, but not glutamate. However, systemic CX717 does not alter these neurotransmitters. CX717 also produced a rapid (up to 1 h) increase of brain-derived neurotrophic factor (BDNF) and a more sustained (up to 6 h) increase of p11. Overall, CX717 appears to possess a rapid but not sustained antidepressant action possibly caused by rapid increases of BDNF and p11.

Keywords: Ampakine; Antidepressant; BDNF; Prefrontal cortex; p11.

PubMed Disclaimer

References

    1. Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61 - PubMed
    1. Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH (2007) Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 32:1888–1902 - PubMed
    1. Duric V, Banasr M, Stockmeier CA, Simen AA, Newton SS, Overholser JC, Jurjus GJ, Dieter L et al (2013) Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. Int J Neuropsychopharmacol 16:69–82 - PubMed
    1. Wisden W, Seeburg PH, Monyer H (2000) AMPA, kainate and NMDA ionotropic glutamate receptor expression – an in situ hybridization atlas. In: Ottersen OP, Storm-Mathisen J (eds) Handbook of Chemical Neuroanatomy, Glutamate, vol 18. Elsevier, Amsterdam, pp. 99–143
    1. Beneyto M, Meador-Woodruff JH (2008) Lamina-specific abnormalities of NMDA receptor-associated postsynaptic protein transcripts in the prefrontal cortex in schizophrenia and bipolar disorder. Neuropsychopharmacology 33:2175–2186 - PubMed

MeSH terms