RespireRx Pharmaceuticals Inc. announced that KRM-II-81, its lead GABAA receptor potentiator (GABAkine), has advanced to the next level of evaluation within the NIH HEAL Initiative® Preclinical Screening Platform for Pain (PSPP) program. The Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, is an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. Launched in April 2018, the initiative is focused on improving prevention and treatment strategies for opioid misuse and addiction, and enhancing pain management.

The PSPP program, part of the NIH HEAL Initiative, evaluates non-opioid assets in a battery of established preclinical pain models. The PSPP program accepts small molecules, biologics, devices, or natural products for evaluation, from researchers in academia and industry worldwide. Emerging data showed that KRM-II-81 blocked pain-like behaviors in rats at doses with minimal or no detectable side effects.

These observations were made with both male and female rats in two measures each, in models of post-incision pain and spinal nerve ligation-induced persistent neuropathic pain. These research findings support prior observations by their and other laboratories that KRM-II-81 is effective in relieving acute, chronic, and neuropathic pain in a number of models without tolerance development or sedation. These data trigger the advancement of KRM-II-81 within the NIH PSPP program where additional disease-specific pain models will be evaluated.

The RespireRx team is led by Dr. Arnold Lippa, RespireRx Executive Chairman, Interim Chief Executive Officer, Interim President and Chief Scientific Officer along with RespireRx Senior Research Fellows, Drs. Jeffrey M. Witkin and Rok Cerne and collaborator, Dr. James M. Cook, in addition to their academic affiliations at Ascension St. Vincent and Indiana University/Purdue University and the University of Wisconsin-Milwaukee, respectively.

The team has extensive expertise in drug discovery and development including the development of novel analgesic drugs and an extensive publication record with a combined total of over 1,000 scientific publications. The team has already profiled the activity of KRM-II-81 in a broad range of preclinical studies where it has displayed a high degree of analgesic activity and is excited at the prospect of advancing the Company?s lead GABAkine toward clinical development. In cellular studies, KRM-II-81 preferentially bound to specific 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 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. Unrelated to the NINDS project, KRM-II-81 has also shown very promising results in multiple animal models of treatment resistant epilepsy and in human translational studies where it reduced epileptiform electrical signaling in brain tissue removed from treatment resistant epileptic patients who underwent surgery.