Antidepressant-Like Effects of CX717, a Positive Allosteric Modulator of AMPA Receptors
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...
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| Veröffentlicht in: | Molecular neurobiology 2020-08, Vol.57 (8), p.3498-3507 |
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| creator | Gordillo-Salas, Marta Pascual-Antón, Raquel Ren, Jun Greer, John Adell, Albert |
| description | 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. |
| doi_str_mv | 10.1007/s12035-020-01954-x |
| format | Article |
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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. 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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.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s12035-020-01954-x</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0570-4931</orcidid></addata></record> |
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| subjects | Allosteric properties Antidepressants Biomedical and Life Sciences Biomedicine Brain-derived neurotrophic factor Cell Biology Dopamine Drugs Glutamatergic transmission Ketamine Monoamines Neurobiology Neurology Neuromodulation Neurosciences Neurotransmitters Norepinephrine Original Article Pyramidal cells Serotonin α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors |
| title | Antidepressant-Like Effects of CX717, a Positive Allosteric Modulator of AMPA Receptors |
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