Algernon Pharmaceuticals Inc (AGNPF)

[medchem]

Cognitive effects of Ifenprodil

Recently published study this month showing that there are positive psychologic effects of Ifenprodil in combination with modulation (decrease) in pro-inflammatory (bad) cytokines (markers of inflammation). My take from this is that patients who are treated with chronic cough might also have increased mood and "feel better" overall, in addition to objectively coughing less. They would likely also cough less because of the modulation of pro-inflammatory effects: here that is observed by a decrease in TNF-alpha, a potent inflammatory marker (it also decreased IL-1B and IL-6 inflammatory markers).

Who knows, maybe we should be doing a trial of this medication for depression also. Or perhaps a better use of this data would be to recognize that capturing mood data as a secondary outcome measure in their study for patients with chronic cough would be useful... The future is bright! The cool part about using repurposed drugs... they have proven safety.

*Note, this is an asian study, nobody is studying this like us in north america*

RATIONALE:

The rapid-onset and long-lasting antidepressant properties of ketamine have prompted investigations into a variety of agents that target N-methyl-D-aspartate receptors (NMDARs) for the treatment of major depressive disorder (MDD). According to the literature, ifenprodil (a GluN2B-containing NMDAR antagonist) can potentiate the antidepressant-like effects of certain antidepressant drugs in mice. Here, we report that a single injection of ifenprodil (3 mg/kg, intraperitoneally (i.p.)) was sufficient to provoke rapid antidepressant-like effects in chronic unpredictable mild stress (CUMS) rats. Moreover, ifenprodil activated mTOR signaling and reversed the CUMS-induced elevation of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a) in the hippocampus after acute administration.

Our data indicate that ifenprodil per se might exert antidepressant-like effects by modulating neuroplasticity and inflammatory processes rather than the typical hormonal factors affected by stressors.


OBJECTIVES:

To explore the potential rapid antidepressant-like effects and mechanisms of ifenprodil, a GluN2B subunit-selective NMDAR antagonist.
METHODS:

Male Sprague-Dawley rats were used in 3 separate experiments. In experiment 1, we used the forced swim test (FST) and sucrose preference test (SPT) to identify the rapid antidepressant-like effects of ifenprodil in chronic unpredictable mild stress (CUMS) rats after acute administration. In experiment 2, we assessed neurochemical changes involved in synaptic plasticity within the hippocampus of CUMS rats. In experiment 3, we assessed the levels of corticosterone in the plasma and proinflammatory cytokines in the hippocampus in CUMS rats after ifenprodil treatment.
RESULTS:

Ifenprodil rapidly ameliorated depressive-like behaviors in the FST and SPT, activated mTOR signaling, dephosphorylated eukaryotic elongation factor 2, enhanced BDNF expression, and promoted the synthesis of the synaptic protein GluA1 synthesis after acute administration. Moreover, ifenprodil reversed the CUMS-induced elevation of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a) in the hippocampus after acute administration.

CONCLUSIONS:

Our data indicate that ifenprodil per se might exert antidepressant-like effects through its effects on neuroplasticity and inflammatory processes rather than the typical hormonal factors affected by stressors.

It has also been used to treat PTSD as seen here...