RespireRx Pharmaceuticals Inc. announced 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 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.