KSEF R&D Excellence: S(-)-Norketamine-Morphine Combination Drug for Treatment of Chronic Pain

  • Holtman, Joseph (PI)
  • Wala, Elzbieta (CoI)

Grants and Contracts Details


Chronic pain affects over 30 million people annually in the US. It is especially prevalent in Kentucky due to the large number of injured workers (coal mining industry, agriculture) and common medical conditions (cancer, diabetes, spinal cord injury, stroke), It has been reported that 41 % of people in Kentucky experience pain on a monthly basis which in 34% of the population is moderate to severe. Currently, opioids (eg. morphine) are the drugs of choice for moderate to severe pain. However, these drugs work poorly for chronic neuropathic pain (eg. diabetic neuropathy, tumor invasion of nerves, spinal cord injury) and have prominent side effects. N-methyl-D-aspartate (NMDA) antagonists have been proposed for neuropathic pain. Ketamine, the only clinically available NMDA-antagonist, has severe side effects (psychosis, sedation, motor impairment). NMDA-antagonists with better analgesic/side effects profiles are needed. We have demonstrated that the novel NMDA-antagonist S(-)-norketamine is analgesic in a rodent model of neuropathic pain and has fewer side effects than ketamine. Furthermore, a pilot experiment combining subanalgesic doses of S(-)- norketamine with low dose morphine demonstrated a synergistic analgesic effect The drug combination was also effective for other types of pain. Side effects of each drug were significantly diminished. No such combination-drug is currently available and its development would represent a significant step forward in the treatment of chronic pain. Our ultimate goal is to create intellectual property and develop a novel combination-drug for chronic pain. Our hypothesis is that a subanalgesic dose of S(-)- norketamine will decrease opioid utilization, enhance analgesia and result in fewer side effects. This combination-drug is likely to be effective in chronic pain of differing etiology. We propose a feasibility study to determine the analgesic efficacy of S(-)- norketamine-morphine combination in well-established models of nociceptive (eg. arthritis) and neuropathic (nerve-injury) pain in rats. Side effects will also be examined. Kev words: Combination drug: Chronic pain; NMDA antagonist; Opioid; Side effects
Effective start/end date1/1/0612/31/06


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