RespireRx Pharmaceuticals Inc. Announces Publication of Book Chapter Describing Novel Analgesic Properties of KRM-II-81
RespireRx Pharmaceuticals Inc. (OTCQB: RSPI) announced the publication of research on KRM-II-81, a novel analgesic, in the book The Neurobiology, Physiology, and Psychology of Pain. This compound selectively potentiates GABAA receptors, showing significant analgesic efficacy without common opioid side effects. KRM-II-81 demonstrated comparable or superior analgesic effects in animal models compared to traditional analgesics, while avoiding tolerance, dependence, and respiratory depression. The company is optimistic about KRM-II-81's potential to address pain management amidst the opioid crisis.
- KRM-II-81 shows strong analgesic efficacy in preclinical studies, comparable to traditional analgesics.
- The compound does not produce tolerance, dependence, respiratory depression, or abuse potential.
- Studies indicate KRM-II-81 may help in treating complex pain conditions that currently lack effective management options.
- None.
Glen Rock, N.J., Nov. 30, 2021 (GLOBE NEWSWIRE) -- RespireRx Pharmaceuticals Inc. (OTCQB: RSPI) (“RespireRx” or the “Company”), a leader in the discovery and development of innovative and revolutionary treatments to combat diseases caused by disruption of neuronal signaling, is pleased to announce that scientists associated with the Company have published a chapter entitled “The orally bioavailable imidazodiazepine, KRM-II-81, is a novel potentiator of α2/3- containing GABAA receptors with analgesic efficacy” in the book The Neurobiology, Physiology, and Psychology of Pain (Academic Press, https://doi.org/10.1016/B978-0-12-820589-1.00011-7). The multidisciplinary team of authors was led by Drs. James M. Cook and Jeffrey M. Witkin, both of whom are RespireRx Research Fellows and Dr. Rok Cerne, RespireRx Senior Research Scientist, in addition to their academic affiliations at University of Wisconsin-Milwaukee and Indiana University/Purdue University, respectively. Authors also include Jodi L. Smith, Janet L. Fisher, Daniel E. Knutson and Lalit K. Golani.
KRM-II-81 is being developed by the Company’s EndeavourRx business unit and is termed a GABAkine because of its ability to amplify inhibitory neurotransmission by selectively potentiating a subset of GABAA receptors, thus producing a unique efficacy and reduced side-effect profile. Preclinical studies have documented its efficacy in a broad array of animal models of interrelated neurological and psychiatric disorders including epilepsy, pain, anxiety, and depression.
As described in the chapter, KRM-II-81 has displayed a high degree of analgesic activity in a broad range of preclinical studies. In cellular studies, KRM-II-81 preferentially bound to certain subtypes of GABAA receptors and boosted the ability of GABA to inhibit pain sensory neurons in the spinal dorsal root ganglia. In intact animal models of acute and chronic 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 important, it did not produce tolerance, dependence, respiratory depression or behavioral changes indicative of abuse liability.
The opioid epidemic has created a crisis in the treatment of acute and chronic pain. While there is no question as to their efficacy, the clinical use of opioids is severely limited due to the rapid development of tolerance, dependence and the production of respiratory depression, the major cause of opioid-induced lethality. Chronic pain is especially difficult to treat due to its complex nature and different etiologies, including injury, surgery, neuropathy, inflammation produced by arthritis or by certain drugs such as cancer chemotherapeutics. For these reasons, better management and control of both acute and chronic pain continues to be a serious need in medical practice.
Dr. Jeffrey Witkin, a senior author of the book chapter said “The renewed efforts to develop improved GABAkines allows the fine-tuned use of the patient’s primary inhibitory neurotransmitter system to help moderate a host of neurological and psychiatric disorders. We are excited about the prospect that this novel GABAkine may give hope to those patients burdened with chronic pain or intractable epilepsy.”
According to Arnold Lippa Ph.D., the Company’s Executive Chairman and Chief Scientific Officer, “We believe that the ability to attenuate both acute and chronic pain combined with a greatly reduced side effect profile, a lack of respiratory depression, tolerance, dependence and abuse potential makes KRM-II-81 a promising clinical lead and a potential advance in pain therapeutics. Pending clinical validation, it is possible that KRM-II-81 might be the non-narcotic analgesic that is widely being sought. Additional results from preliminary chemistry, metabolism and pharmacokinetic studies warrant its further development.”
About RespireRx Pharmaceuticals Inc.
RespireRx Pharmaceuticals Inc. is a leader in the discovery and development of medicines for the treatment of psychiatric and neurological disorders, with a focus on treatment options that address conditions affecting millions of people, but for which there are few or poor treatment options, including obstructive sleep apnea (“OSA”), attention deficit hyperactivity disorder (“ADHD”), epilepsy, chronic pain and recovery from spinal cord injury (“SCI”), as well as certain neurological orphan diseases. RespireRx is developing a pipeline of new drug products based on our broad patent portfolios for two drug platforms: (i) pharmaceutical cannabinoids, which include dronabinol, a synthetic form of ∆9-tetrahydrocannabinol (“Δ9-THC”) that acts upon the nervous system’s endogenous cannabinoid receptors and (ii) neuromodulators, which include AMPAkines and GABAkines, proprietary compounds that positively modulate (positive allosteric modulators or “PAMs”) AMPA-type glutamate receptors and GABAA receptors, respectively.
The Company 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.
ResolutionRx: Pharmaceutical Cannabinoids.
Dronabinol. RespireRx is developing dronabinol, ∆-9-THC, a synthetic version of the naturally occurring substance in the cannabis plant, for the treatment of OSA, a serious respiratory disorder that impacts an estimated 29.4 million people in the United States according to the American Academy of Sleep Medicine (“AASM”), published in August 2016. OSA has been linked to increased risk for hypertension, heart failure, depression, and diabetes, and has an annual economic cost in the United States of
Two Phase 2 clinical trials have been completed demonstrating the ability of dronabinol to significantly reduce the symptoms of OSA and, subject to raising sufficient financing (of which no assurance can be provided) and pending the outcome of an intended meeting with the FDA, RespireRx believes that it will be able to commence a pharmacokinetic study for a to-be-developed new formulation followed by a Phase 3 clinical study for the treatment of OSA with the new formulation. Because dronabinol is already FDA approved for the treatment of AIDS related anorexia and chemotherapy induced nausea and vomiting, the Company further believes that its re-purposing strategy would only require approval by the FDA of a 505(b)(2) new drug application (“NDA”), an efficient regulatory pathway that allows the use of publicly available data.
EndeavourRx: Neuromodulators
GABAkines. Under a License Agreement with the University of Wisconsin-Milwaukee Research Foundation, Inc. (“UWMRF”), an affiliate of the University of Wisconsin-Milwaukee, RespireRx has licensed rights to certain selectively acting GABAkines that have shown impressive activity in a broad range of animal models of pain, refractory/drug resistant epilepsy and other convulsant disorders, as well as in brain tissue samples obtained from epileptic patients. Epilepsy is a chronic and highly prevalent neurological disorder that affects millions of people world-wide. While many anticonvulsant drugs have been approved to decrease seizure probability, seizures are not well controlled and, in as many as 60
AMPAkines. Through an extensive translational research effort from the cellular level through Phase 2 clinical trials, the Company 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. From our AMPAkine platform, 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 adults with ADHD. At present, the major pharmacotherapies available for ADHD are made up of two types of drugs. Stimulants, such as amphetamine, rapidly produce robust effects, but suffer from side effects typical of stimulants, including tolerance, dependence, withdrawal and abuse. For these reasons, stimulants are scheduled by the FDA. Non-stimulants, such as Straterra® (atomoxetine) tend to be less effective than stimulants, with a much longer (approximately 4 – 8 week) latency to onset of action. In a number of animal and human studies, CX717 and other AMPAkines did not display any stimulant properties typically associated with drugs like amphetamine. In the Phase 2 ADHD clinical trial, statistically significant therapeutic effects were observed within one week. Therefore, we believe AMPAkines may represent a novel, non-stimulant treatment for ADHD with a more rapid onset of action than alternative non-stimulant treatment options.
Additional information about RespireRx and the matters discussed herein can be obtained on the Company’s web-site at www.RespireRx.com or in the Company’s filings with the Securities and Exchange Commission at www.sec.gov.
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For more information about the risks and uncertainties the Company faces, see “Item 1A. Risk Factors” in our recent annual report on Form 10-K as of December 31, 2020. Forward-looking statements speak only as of the date they are made. The Company does not undertake and specifically declines any obligation to update any forward-looking statements or to publicly announce the results of any revisions to any statements to reflect new information or future events or developments. We advise investors to consult any further disclosures we may make on related subjects in our most recent annual report on Form 10-K for the year ended December 31, 2020 and any subsequent documents we file with or furnish to the SEC.
Company Contact:
Jeff Margolis
Senior Vice President, Chief Financial Officer, Treasurer and Secretary
Telephone: (917) 834-7206
E-mail: jmargolis@respirerx.com
RespireRx Pharmaceuticals Inc.
126 Valley Road,
Suite C,
Glen Rock, NJ 07452
www.respirerx.com
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