RespireRx Pharmaceuticals Inc. Announces Discovery of a New GABAkine Neuromodulator that Protects Against Seizures and Lethality
BY GlobeNewswire
— 8:00 AM ET 03/16/2022
Glen Rock, N.J., March 16, 2022 (GLOBE NEWSWIRE) -- RespireRx Pharmaceuticals Inc. ( 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 manuscript detailing the pharmacology of its newest asset, D5-KRM-II-81. The paper titled Metabolism, pharmacokinetics, and anticonvulsant activity of a deuterated analog of the a2/3-selective GABAkine KRM-II-81 in Biopharmaceutics and Drug Disposition. 2022 Feb 22. doi: 10.1002/bdd.2313. Epub ahead of print. PMID: 35194800.
The multidisciplinary team of authors was led by Dr. Jeffrey M. Witkin, a senior research fellow at RespireRx with contributions from academic collaborators at the University of Wisconsin-Milwaukee, Ascension St. Vincent and Indiana University/Purdue University, and the University of Belgrade in Serbia. Authors also include Arnold Lippa, RespireRx Executive Chairman, Interim President and Interim Chief Executive Officer and Chief Scientific Officer. Dr. Lippa is a pioneer in this field since its inception being the first to identify compounds with anxiolytic effects without sedation and to bring them into clinical development (e.g., ocinaplon) while another co-author, Dr. James M. Cook has been inventing key compounds for modulation of GABA-A receptors for several decades.
Since the FDA approval of brexanolone (Zulresso®) for post-partum depression in 2019, several new potentiators of GABA (GABAkines) have entered into the pharmaceutical pipeline. KRM-II-81, originally synthesized by Dr. Cook, is being developed by EndeavourRx, the Company’s neuromodulator business unit, because of its ability to selectively amplify inhibitory neurotransmission at a highly, specific subset of GABAA receptors, thus producing a unique efficacy profile with reduced side effects. The Company currently is focusing on developing KRM-II-81 for the treatment of epilepsy and acute and chronic pain which includes inflammatory and neuropathic pain, which we refer to simply as pain. The findings of broad antiepileptic activity in models of pharmacoresistant epilepsy and in models of pain have encouraged the development of this compound.
D5-KRM-II-81 a structurally related analog is being evaluated by EndeavourRx as a potent, and orally-bioavailable backup that will be used as needed as KRM-II-81 enters its clinical development. Doses of D5-KRM-II-81 as low as 2 mg/kg provided enduring exposure of plasma and brain of rats after oral administration. Importantly, like KRM-II-81, D5-KRM-II-81 completely prevented clonic seizures, tonic seizures, and lethality induced by the GABA receptor antagonist chemoconvulsant pentylenetetrazol. Experimental work in human epileptic brain tissue from patients that are resistant to standard of care antiepileptic medicines is ongoing.
Senior author Dr. Witkin commented, “The antiepileptic potential discovered for D5-KRM-II-81 allows this new orally-bioavailable analog to assist with our drug development efforts in pharmacoresistant epilepsy and pain. Given the large unmet medical need in both of these areas, we are excited to have this new structural analog in our hands.”
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