Hello Once Again,
As one reviews Ifendropil, it becomes more and more pertinent as it being an active receptor antagonist. There is so much much more for us to know of the chemistry make up that makes us human.
The interaction of systems,eg. neural(nervous) & immune systems are increasingly being studied. With more studies, humanity may find how closely the systems do work together as a team for our well being mental & health.
The NDMA receptor importance is being highlighted ever more so, with further research, as being a critical part of our general overall physical & well being makeup.
Time & hard work will reveal the truths.
Keep in mind too that Ifendropil can be used in conjunction, as seen below with great success, with other therapeutics too.
The following is another front for the use of Ifendropil:
Small-cell lung cancer growth inhibition: synergism between NMDA receptor blockade and chemotherapy Authors North WG, Liu F, Dragnev KH, Demidenko E
Received 14 August 2018
Accepted for publication 5 December 2018
Published 23 January 2019 Volume 2019:11 Pages 15—23
Background: Small-cell lung cancer (SCLC) has a poor prognosis since there is currently no effective therapy for commonly recurring disease. In our previous study, both primary and recurrent human tumors have been shown to express functional N-methyl-D-aspartate (NMDA) receptors, and blockade of these receptors with GluN1 and GluN2B antagonists decreased tumor cell viability in vitro, and growth of tumor xenografts in nu/nu mice.
Materials and methods: In this study, we examine the influence of the GluN2B antagonist ifenprodil and the channel-blocker antagonist memantine, on cell viability and growth of tumor xenografts of recurrent SCLC (rSCLC) in mice.
Results: Both antagonists significantly reduced cell viability and levels of components of the ERK1/2 pathway, increased apoptosis, and at very safe levels significantly reduced the growth of tumors in mice. Each antagonist and topotecan had additive effects to reduce cell viability with significant synergy demonstrated for the case of memantine. More significantly, combination treatments of xenografts in mice with ifenprodil and the chemotherapeutic agent topotecan produced clear additive effects that completely stopped tumor growth. Moreover, the ifenprodil and topotecan combination showed excellent supra-addition or synergy of inhibition for tumors ≤300 mm in size (P=4.7E−4). Combination treatment of memantine with topotecan also showed clear addition but, unlike ifenprodil, no synergy for the doses chosen.
Conclusion: Since topotecan is a drug of choice for treatment of rSCLC, our findings suggest that combining this agent with NMDA receptor blockade using the GluN2B antagonist, ifenprodil, will significantly improve patient outcomes.
Conclusion
Regarding mechanisms, we have previously shown the presence of GluN1 and GluN2B proteins for NMDA receptors on SCLC so, despite both drugs having other actions, it is likely that memantine is operating as an antagonist through interaction with GluN1 and ifenprodil as an antagonist through interaction with both GluN1 and GluN2B.11,12 Others9,10 have shown that blockade of NMDA receptors with other antagonists in lung adenocarcinoma and other cancer cells produced a substantial reduction in phosphorylated p42/44MAPK, and 24 hour incubations with either ifenprodil or memantine produced similar reductions in phosphor-p42/44MAPK, while each antagonist reduced total p42/44MAPK in the same differential substantial manner by reducing p42MAPK to about one-third while increasing p44MAPK about twofold. However, the enhanced effects of combination on cell viability seen with topotecan did not appear to involve the ERK1/2 cascade, because the chemotherapeutic agent only seemed to marginally affect this system and not add to the effects seen with the antagonists.
Both ifenprodil and memantine treatments in vitro substantially reduced cell levels of the intact DNA repair protein PARP in rSCLC cells when corrected for GAPDH, while increasing PARP1 breakdown fivefold to the 89Kd product, representing substantially increased caspase activity. This showed that the antagonists were promoting cancer cell apoptosis ( Apoptosis removes cells during development. It also eliminates pre-cancerous and virus-infected cells, although “successful” cancer cells manage to escape apoptosis so they can continue dividing. Apoptosis maintains the balance of cells in the human body and is particularly important in the immune system. ) while reducing DNA repair through PARP1. Pietanza et al7 have reported common overexpression of the DNA repair proteins PARP1, Chk1, BRCA-1, and RAD51 in SCLC and suggest that this might represent primary resistance to agents like topotecan, which is an inhibitor of topoisomerase-1 and reduces repair of double-stranded DNA breaks. Reducing levels of DNA repair proteins, as shown here for active PARP1, could be one mechanism through which NMDA antagonists enhance the actions of topotecan.
While the mechanism for selective synergy of NMDA receptor blockade with topotecan is still to be resolved, it is clear that ifenprodil and topotecan together seem to exert a profound effect on tumor xenografts of rSCLC. The data from this and our other studies allow us to conclude that there is good reason outcomes for patients with this disease could be significantly improved by including NMDA receptor blockade by ifenprodil with currently preferred topotecan treatment.
Best wishes to All, good health,
Sincerely,
Topseeker
P.S. Connecting the dots of how we are doing health wise, we may find that the NMDA receptor may need at times antagonists, such as, Ifendropil, to perhaps maintain a more healthy regular flow of eg. ions vs chaotic flows caused by perhaps, cancers, covids, etc. IMO. Topseeker