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YES LOL RSPI my mistake RFK jr could be good for RSPI
By RITE you mean RSPI? Maybe sometimes things have to get worse before they can get better.
So might RSPI, a zombie security backed by a load of stellar, but underdog neuroscience, that can mostly only be traded by Canadians in a sandbox restricted for essentially cronies, a few neurodivergent misfits, and some retirees rise from its ashes and run 50000% to a dollar? Well if any ticker can, it’s it.
By RITE you mean RSPI? Maybe sometimes things have to get worse before they can get better.
It would be nice to be back trading and seeing this RSPI have days like Friday on another stock I have 9.96 3.05 (44.14%) GLTA
Acute ampakines increase voiding function and coordination in a rat model of SCI
Sabhya Rana , Firoj Alom , Robert C Martinez , David D Fuller , and Aaron D Mickle
Elife, 2024
Neurogenic bladder dysfunction causes urological complications and reduces the quality of life in persons with spinal cord injury (SCI). Glutamatergic signaling via AMPA receptors is fundamentally important to the neural circuits controlling bladder voiding. Ampakines are positive allosteric modulators of AMPA receptors that can enhance the function of glutamatergic neural circuits after SCI. We hypothesized that ampakines can acutely stimulate bladder voiding that has been impaired due to thoracic contusion SCI. Adult female Sprague–Dawley rats received a unilateral contusion of the T9 spinal cord (n = 10). Bladder function (cystometry) and coordination with the external urethral sphincter (EUS) were assessed 5 d post-SCI under urethane anesthesia. Data were compared to responses in spinal-intact rats (n = 8). The ‘low-impact’ ampakine CX1739 (5, 10, or 15 mg/kg) or vehicle (2-hydroxypropyl-beta-cyclodextrin [HPCD]) was administered intravenously. The HPCD vehicle had no discernible impact on voiding. In contrast, following CX1739, the pressure threshold for inducing bladder contraction, voided volume, and the interval between bladder contractions were significantly reduced. These responses occurred in a dose-dependent manner. We conclude that modulating AMPA receptor function using ampakines can rapidly improve bladder-voiding capability at subacute time points following contusion SCI. These results may provide a new and translatable method for therapeutic targeting of bladder dysfunction acutely after SCI
RespireRx pharm. $RSPI mentioned in new market report:
RHYTHM SLEEP DISORDERS MARKET REPORT & FORECAST 2024-2031
Report ID: 1840020 | Published Date: Mar 2025 | No. of Page: 87
https://www.reliablebusinessarena.com/toc/1840020#companiescovered
Its great that they are getting out there attempting to draw attention and interest towards their candidates...
Just waiting on that one big deal to set off an avalanche of good tidings for the pipeline.. Another week of silence, but also another week closer.
Well the DOD funding is for phase 2 SCI using CX1739 so it all runs together. I guess my question is more along the lines of what is holding up initiating the phase 2 for SCI.
This poster presentation relates directly to the DoD trial. I don’t see on the site the names of the presenters, and I’m not sure the info is available yet.
LT - This publication appears not have anything to do with the DoD.. RSPI, as I have surmised previously provided their molecules to university biology departments all over the world, Notice that none of the authors are associated with RSPI although I recall there is collaboration with UF. RSPI will use this publication for preclinical support of CX1739 as a molecule with great potential in their ampakine platform.
I guess the other thing is the entire zoo of ampakines...
Would love to see this science team have the opportunity and flexibility business/funding wise to explore past ampakines with newer technology and newer learnings that can once again make them powerful and viable compounds. Given the current state, it is hard to say if that is even a desire however.
I still think KRM-ll-81 is the king maker here and once that gets a deal in place, hopefully soon after exiting NIH IND enabling for pain and with whatever SBIR funding and IND support is needed for epilepsy. Once they can lock down a large deal for that compound, I think it is possible they can enter the zoo and look around.
Judging by the deal SAN711 got after a phase 1, I expect KRM-ll-81 can be as significant or greater deal now. It may not have any human clinical data yet, but the design and premier preclinical look of the compound might label it best-in-class gabakine for development of epilepsy and pain mitigation therapies...
meixatech,
What would you speculate is the reason this was stated in the shareholder letter... "The Department of Defense grant to Shirley Ryan AbilityLab for a spinal cord injury clinical trial with our CX-1739 compound and our participation has proven difficult to implement and commence."
Is it additional funding or finding enough patients to participate, etc? Or something more related to the compounding? I am also curious is the additional grant application they mentioned would be for ampakines for ADHD. I would speculate it would since ADHD is something they continually reference as higher on priority in their communications and such, and they have good initial clinical results to parlay into a potential large market and need.
Acute ampakines increase voiding function and coordination in a rat model of SCI
Sabhya Rana, Firoj Alom, Robert C Martinez, David D Fuller, Aaron D Mickleauthor has email address
Department of Physical Therapy, University of Florida, Gainesville, FL, 32610
https://doi.org/10.7554/eLife.89767.2
Abstract
Neurogenic bladder dysfunction causes urological complications and reduces the quality of life in persons with spinal cord injury (SCI). Glutamatergic signaling via AMPA receptors is fundamentally important to the neural circuits controlling bladder voiding. Ampakines are positive allosteric modulators of AMPA receptors that can enhance the function of glutamatergic neural circuits after SCI. We hypothesized that ampakines can acutely stimulate bladder voiding that has been impaired due to thoracic contusion SCI. Adult female Sprague Dawley rats received a unilateral contusion of the T9 spinal cord (n=10). Bladder function (cystometry) and coordination with the external urethral sphincter (EUS) were assessed five days post-SCI under urethane anesthesia. Data were compared to responses in spinal intact rats (n=8). The “low impact” ampakine CX1739 (5, 10, or 15 mg/kg) or vehicle (HPCD) was administered intravenously. The HPCD vehicle had no discernable impact on voiding. In contrast, following CX1739, the pressure threshold for inducing bladder contraction, voided volume, and the interval between bladder contractions were significantly reduced. These responses occurred in a dose-dependent manner. We conclude that modulating AMPA receptor function using ampakines can rapidly improve bladder voiding capability at sub-acute time points following contusion SCI. These results may provide a new and translatable method for therapeutic targeting of bladder dysfunction acutely after SCI.
I don't know about that high of valuation, as I think they would have to get into phase 3 for KRM-ll-81 and have it looking good for both pain and epilepsy indications.. Possible, but a long ways out. They need to focus on the immediate term and get the ship righted and on a solid path. I am hoping a BP steps in and does a deal exiting the NIH IND enabling studies. There is enough historical evidence out there as to the success gabakines can have at least in phase 1 level trials and these with selectivity have little concern for side effects in early stage trials. KRM-ll-81 looks like it might be superior in the class. If they can strike a significant deal with upfront cash and milestone payments long term, they can then focus their efforts on developing their other candidates for epilepsy, ADHD, OSA, orphan indications... and retain more equity in those candidates...
Or possibly just sell one of the other platforms and utilize resources to retain equity in the remaining two and push development. Their efforts, although smart on the science end, have stretched far to thin what the business end is capable of. IMO.
That's true . If the drug works we may see dollars thru a buyout !
I might sell half at that level.
The rest I might want to have stick around to see if KRM-ll-81 truly becomes a breakthrough drug.
How about 5 answers to questions?
Is the holdup in the OSA program related to lack of clarity on re-scheduling cannibas in the USA?
Will SBIR grant funding you mentioned you are applying for additional ampakine development be for ADHD medical indication or something else?
Is CX-717 patent life a concern and would CX-1739 (superior, longer patent?) "easily" substitute for any potential phase 2 program in ADHD?
Is the gabakine grant funding in motion for IND enabling of epilepsy phase 1 trials only and pain IND enablement being handled by NIH?
Using an excerpt from a publication.. "SAN711, an a3-preferring GABAkine, and the a2/3-preferring GABAkine, KRM-II-81, bring new therapeutic promise..."
Is the feeling that "a2/3-preferring" is a big advantage as it makes the compound more efficacious for a variety of medical indications pain & epilepsy, or better yet how do you feel KRM-ll-81 stacks up to SAN711, which happened to ink a very nice development deal for Saniona from Acadia late last year....
A lot of catalysts looming out there... IMO, there will be a snowball effect at some point. GLTA, back to not harping on and on about the EM and the website..
For .10 they can have them 😆
"Experts" who want our shares of course!
You sound like Musk.
Jeff, please email shareholders back with 5 bullet points of what you accomplished on the job last week.
This sort of small lot transaction is usually followed by a large lot transaction at the 0.002 level. So in the EM it seems it’s more useful to look at the average price a single share trades for, regardless of lot size.
Who sells 797 shares at .0006 ? Come on now 😞
https://www.physiology.org/professional-development/meetings-events/american-physiology-summit/program?SSO=Y#Friday
We are pleased to present the program for the American Physiology Summit (#APS2025), April 24–27, 2025.
5:15 PM – 7:00 PM EDT
Stroke, Spinal Cord Injury and Reparative Plasticity Poster Session
Conv. Ctr., Posters, PhysioHub
10 Sub-sessions
5:15 PM – 5:15 PM EDT
(Poster F449) Impact of ampakine CX1739 on histological neuronal counts after acute cervical spinal cord injury (SCI)
Conv. Ctr., Posters, PhysioHub
Part of Stroke, Spinal Cord Injury and Reparative Plasticity Poster Session
Wowzers!!! The implications of cancer treatment with CX614 should in itself be a game changer and not just for gliablastoma treatment.
What a great way to look at our situation here, faith it is !!! GLTA.....
You are exactly right.
This forum has been great to help understand a bunch about the science, the paths and where it all may lead. I think criticism of the current situation is more than fair as the frustration and testing of patience should be very understandable to all. Sometimes however, it may just be best to take a leap of faith, walk away from the frustration and just hope for the best. As the company states...
"Together, we can advance life-changing therapies, create value for our investors, and positively impact the lives of patients worldwide." And the most successful endeavours, the most successful companies generally find much truth in the word "Together".
Wishing good luck and good health to all here...
AMPA Receptor Modulation in the Treatment of High-Grade Glioma: Translating Good Science into Better Outcomes
Daniel P. Radin
Stony Brook Medical Scientist Training Program, Renaissance School of Medicine at Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, USA
Pharmaceuticals 2025, 18(3), 384; https://doi.org/10.3390/ph18030384 (registering DOI)
Submission received: 15 January 2025 / Revised: 24 February 2025 / Accepted: 28 February 2025 / Published: 8 March 2025
Abstract
Glioblastoma (GB) treatment, despite consisting of surgical resection paired with radiation, temozolomide chemotherapy and tumor-treating fields, yields a median survival of 15–20 months. One of the more recently appreciated hallmarks of GB aggressiveness is the co-opting of neurotransmitter signaling mechanisms that normally sustain excitatory synaptic communication in the CNS. AMPA-glutamate receptor (AMPAR) signaling governs the majority of excitatory synaptic activity in the mammalian brain. AMPAR activation in glioma cells activates cellular pathways that enhance proliferation and invasion and confer resistance to approved GB therapeutics. In addition, this review places a specific emphasis on discussing the redefined GB cytoarchitecture that consists of neuron-to-glioma cell synapses, whose oncogenic activity is driven by AMPAR activation on glioma cells, and the discovery of tumor microtubes, which propagate calcium signals throughout the tumor network in order to enhance resistance to complete surgical resection and radiotherapy. These new discoveries notwithstanding, some evidence suggests that AMPAR activation can produce excitotoxicity in tumor cells. This disparity warrants a closer examination at how AMPAR modulation can be leveraged to produce more durable outcomes in the treatment of GB and tumors in peripheral organs that express AMPAR.
Keywords:
AMPA receptor; BDNF; glutamate; neurogliomal synapse; tumor microenvironment; tumor microtube
…
.
Stemming from this work, we recognized that if fluoxetine bound AMPARs at the agonist binding site, its pharmacological actions might be enhanced by concomitant treatment with an ampakine. We first demonstrated that fluoxetine possesses robust oncolytic activity to GB cells, colorectal cancer cells, and pancreas cancer cells in vitro, with all three cell lines having been previously shown to express functional AMPARs. Our subsequent studies demonstrated that CX614, an ampakine that strongly offsets receptor desensitization and prolongs agonist-induced currents [104], also reduces cancer cell viability [66]. Two ampakines that exert little effect on desensitization, CX717 and CX1739, did not alter cancer cell viability [66]. These data demonstrated that offsetting AMPAR desensitization, and in turn inducing excitotoxicity, is necessary to inhibit cancer cell viability whether the cancer cells stem from the CNS or from peripheral organs. Finally, we showed that treating all three cancer cell lines with CX614, then adding fluoxetine to the culture media five minutes later resulted in a synergistic reduction in cell viability [66], providing more evidence that fluoxetine may be inducing its oncolytic effects by AMPAR activation and subsequent excitotoxicity.
Doesn’t add up for anyone.. not when they have a “remarkable” drug candidate successful in every model of pain and deep into IND enabling with the NIH..
They have to be getting closer to culminating the IND enabling for pain as well as hearing confirmation of grant funding for IND support for epilepsy. Pressure to fix the mess is only going to grow.. there are clearly plenty of eyes watching this one..
100% agreement there LT …. They had ample opportunity to fund at that point but pointedly ran into the expert market after keeping up to date religiously prior to that ? Doesn’t add up in a good way.
This holding has been so frustrating, many of us having $$$$ tied up in this company with so many what ifs!! PATIENCE being tested that's for sure. Hope for the best !!!
I doubt that. If there is any deal in the works it will be some type of license deal upfront with milestones and control of the candidate in the hands of BP or similar.
What kind of impression is made with the lack of communication/strategy and professional presentation on top of allowing your company to "trade" on this obscure expert market? Would any funding source trust leadership to captain the ship? The DOD phase 2 news created roughly what 3-4 million in dollar volume over the course of two trading sessions. Does anyone really believe there could not have been preparations to easily fund the minor amount needed to complete SEC filings and really spend a few bucks upgrading the professional look?
Maybe any potential deal coming is an absolute monster. I think KRM-ll-81 has that look to it. But regardless deal or no deal this EM is damaging to retail and really all stakeholders as time keeps ticking away on the patent life of assets as well as adds to the debt as do any convertibles now jump to a default rate on this obscure market? That is on top of as you continually have mentioned what type of impression does this whole ordeal leave to potential partners and collaborators? What type of opportunities have been lost?
To quote others here.. "I don't get it."
Well this company and RNVA have a lot of things in common with each other.
Maybe a buyout with a cause that they stay aboard to run the trials, and see it thru.
For sure . Lottery ticket because one never knows.
Yeah may just be a dream...
I'll get off the soap box to make room for others... lol.
GLTA
Simply it would help them out alot if they had some professional leadership.
People cannot continue to make excuse after excuse for all that is lacking on the communication and presentation front and the lack of solidifying a financial path or even strategy when these candidates are now at clinical stage! And they are still fooling around on this expert market. Going to be missing 2 10-k's very soon! They should have just financed the money and stayed current a year ago and develop a professional communication and presentation strategy to put this company and their assets on the map. They would be in much better position with preclinical studies maturing and such and much higher stock price to add flexibility in their efforts as well as be able to provide a much better "look" to potential partners and financiers. I don't know what this current strategy is.
"When" this does come out of EM one never knows . Maybe a massive buy out or buyback . Gotta dream big 😀
Who wouldn't want these premier assets to be traded amongst experts!
Why not . It's in EM . In this case you never know 😀
I thought you were going for a penny... what made you try for 10x that? lol....
My shares are for sale daily at .10 cents !
Yeah. That PhD thesis which is no longer posted noted that he could not publish until 2026. I believe that was out of the UK. I am not sure if all universities require peer-revied publication to award a PhD, but UCSD sure did for my daughter. Implies that PhD candidate will not be awarded his PhD until 2026 and also access to CX9292 had a NDA associated. CX929 does not appear to have patent protection.
I don’t think they have any patent protection on old compounds academics may be studying..
I don't disagree. I'm boggled just as much.
It would help them alot to come out and say they have NDA's in place. That alone would would speak volume to the shareholder IMO. It is completely legal to say they are involved in NDA(s) . GLTA
That's what I have been saying for months. I believe Lippa, Cerna and associates have made their compounds available to universities around the world. The prices are truly cheap. I suspect there is an NDA agreement attached. So, as I said before, RSPI is getting first class, worldwide research on the cheap. The most innovative research comes from universities which RSPI has tapped into.
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RespireRx Pharmaceuticals Inc. and its subsidiaries and business units are discovering and developing medicines for the treatment of psychiatric and neurological disorders, with a focus on treatments that address conditions affecting millions of people, but for which there are few or poor treatment options, including epilepsy, pain, attention deficit hyperactivity disorder (“ADHD”), recovery from spinal cord injury (“SCI”), certain neurological orphan diseases and obstructive sleep apnea (“OSA”). The RespireRx Group is developing a pipeline of new and repurposed drug products based on our broad patent portfolios for two drug platforms: (i) neuromodulators, which include GABAkines and AMPAkines, proprietary chemical entities that positively modulate (positive allosteric modulators or “PAMs”) GABAA receptors and AMPA-type glutamate receptors, respectively, and (ii) pharmaceutical cannabinoids, which include dronabinol, a synthetic compound that acts upon the nervous system’s endogenous cannabinoid receptors and
The RespireRx Group holds exclusive licenses and owns patents and patent applications or rights thereto for certain families of chemical compounds that claim the chemical structures and their uses in the treatment of a variety of disorders, as well as claims for novel uses of known drugs.
EndeavourRx: Neuromodulators
GABAkines. Under a License Agreement with the University of Wisconsin-Milwaukee Research Foundation, Inc. (“UWMRF”) and on behalf of its EndeavourRx business unit, RespireRx has licensed rights to certain selectively acting GABAkines because of their ability to selectively amplify inhibitory neurotransmission at a highly specific subset of GABAA receptors, thus producing a unique efficacy profile with reduced side effects. Preclinical studies have documented their efficacy in a broad array of animal models of interrelated neurological and psychiatric disorders including epilepsy, pain, anxiety, and depression in the absence of or with greatly reduced propensity to produce sedation, motor-impairment, tolerance, dependence and abuse. EndeavourRx currently is focusing on developing KRM-II-81 for the treatment of epilepsy and pain.
KRM-II-81 has displayed a high degree of anti-convulsant activity in a broad range of preclinical studies, including in treatment resistant and pharmaco-resistant models. Not only was KRM-II-81 highly effective in these models, but pharmaco-resistance or tolerance did not develop to its anti-convulsant properties. These latter results are particularly important because pharmaco-resistance occurs when medications that once controlled seizures lose efficacy as a result of chronic use and it is a principal reason some epileptic patients require brain surgery to control their seizures. In support of its potential clinical efficacy, translational studies have demonstrated the ability of KRM-II-81 to dramatically reduce epileptiform electrical activity when administered in situ to brain slices excised from treatment resistant epileptic patients undergoing surgery.
In addition, KRM-II-81 has displayed a high degree of analgesic activity in a broad range of preclinical studies. In intact animal models of pain, the analgesic efficacy of KRM-II-81 was comparable to or greater than commonly used analgesics. At the same time, KRM-II-81 did not display side effects such as sedation and motor impairment, but even more importantly, it did not produce tolerance, dependence, respiratory depression or behavioral changes indicative of abuse liability, which are produced by opioid narcotics and are at the heart of the opioid epidemic.
AMPAkines. Through an extensive translational research effort from the cellular level through Phase 2 clinical trials, RespireRx has developed a family of novel, low impact AMPAkines, including CX717, CX1739 and CX1942 that may have clinical application in the treatment of CNS-driven neurobehavioral and cognitive disorders, spinal cord injury, neurological diseases, and certain orphan indications. Our lead clinical compounds, CX717 and CX1739, have successfully completed multiple Phase 1 safety trials. Both compounds have also completed Phase 2 proof of concept trials demonstrating target engagement, by antagonizing the ability of opioids to induce respiratory depression.
AMPAkines have demonstrated positive activity in animal models of ADHD, results that have been extended translationally into statistically significant improvement of symptoms observed in a Phase 2 human clinical trial of CX717 in adult patients with ADHD. Statistically significant therapeutic effects were observed within one week. We believe AMPAkines may represent a novel, non-stimulant treatment for ADHD with a more rapid onset of action than alternative non-stimulants, such as Straterra® (atomoxetine), and without the drawbacks of amphetamine-type stimulants.
In a series of important studies funded by grants from the National Institutes of Health and published in a number of peer reviewed articles, Dr. David Fuller (University of Florida), a long-time RespireRx collaborator, has demonstrated the ability of CX1739 and CX717, RespireRx’s lead AMPAkines, to improve motor nerve activity and muscle function in a number of animal models of spinal cord injury (SCI).
Form Type | Received | Period End Date | Report |
---|---|---|---|
8-K | 09/06/2024 | 08/30/2024 | PDFRTFHTMLXLS |
8-K | 08/02/2024 | 07/29/2024 | PDFRTFHTMLXLS |
8-K | 07/08/2024 | 07/02/2024 | PDFRTFHTMLXLS |
8-K | 05/29/2024 | 05/29/2024 | PDFRTFHTMLXLS |
8-K | 04/16/2024 | 04/10/2024 | PDFRTFHTMLXLS |
NT 10-K | 04/01/2024 | 12/31/2023 | PDFRTFHTMLXLS |
8-K | 02/02/2024 | 01/30/2024 | PDFRTFHTMLXLS |
8-K | 01/22/2024 | 01/18/2024 | PDFRTFHTMLXLS |
8-K | 12/11/2023 | 12/06/2023 | PDFRTFHTMLXLS |
10-Q | 11/17/2023 | 09/30/2023 | PDFRTFHTMLXLS |
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