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

Molecular Neurobiology
Marta Gordillo-SalasAlbert Adell

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 poss...Continue Reading

References

Jan 1, 1987·Acta Neuropathologica·H Benveniste, N H Diemer
Aug 1, 1994·Journal of Neurochemistry·H P Jedema, B Moghaddam
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·S RambozR Hen
Jun 19, 2001·Neuropharmacology·X LiP Skolnick
Dec 26, 2001·The Journal of Pharmacology and Experimental Therapeutics·Zheng-Xiong XiPeter W Kalivas
Apr 18, 2002·European Journal of Pharmacology·Richard J KnappEwa Malatynska
Sep 6, 2002·Neuropharmacology·Marzena MackowiakPhil Skolnick
Nov 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Amy C AraiMarkus Kessler
Jun 27, 2003·Cellular and Molecular Neurobiology·Xia LiPhil Skolnick
Dec 20, 2003·Annals of the New York Academy of Sciences·Roberto I Melendez, Peter W Kalivas
Mar 8, 2005·Neuron·Helen S MaybergSidney H Kennedy
Dec 20, 2005·Current Opinion in Pharmacology·Gary Lynch
Jan 10, 2006·Science·Per SvenningssonPaul Greengard
Jan 31, 2006·Biochemical Pharmacology·Andrew AltJeffrey M Witkin
Jan 24, 2007·Nature Reviews. Neuroscience·Victor A DerkachThomas R Soderling
Feb 15, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Monica BeneytoJames H Meador-Woodruff
Oct 25, 2007·Aviation, Space, and Environmental Medicine·Nancy J WesenstenThomas J Balkin
Nov 23, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Monica Beneyto, James H Meador-Woodruff
Dec 17, 2008·The Journal of Cell Biology·Irina NikonenkoDominique Muller
Jul 10, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hussam JourdiMichel Baudry
Feb 16, 2010·Neuron·Jesse W Richardson-JonesE David Leonardo
Jul 2, 2010·Biological Psychiatry·Jennifer L Warner-SchmidtPaul Greengard
Dec 3, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Herbert E CovingtonEric J Nestler
Dec 21, 2010·Journal of Neuroscience Methods·T J MezadriC Lino-de-Oliveira
Aug 16, 2011·Neurochemistry International·Alessandro BarbonSergio Barlati
Feb 22, 2012·The International Journal of Neuropsychopharmacology·Vanja DuricRonald S Duman
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jennifer L Warner-SchmidtPaul Greengard
Jul 28, 2012·Journal of Applied Physiology·Jun RenJohn J Greer

❮ Previous
Next ❯

Citations

Mar 14, 2021·Purinergic Signalling·Priscila B RosaAna Lúcia S Rodrigues
Apr 1, 2021·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Jana Ruda-KucerovaYousef Tizabi
Jun 19, 2021·Biomedit︠s︡inskai︠a︡ khimii︠a︡·E V RadchenkoV A Palyulin

❮ Previous
Next ❯

Software Mentioned

maze
Any
Image Studio Lite

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.