A new landmark in the treatment of chronic pain

Reckitt & Colman

Cutting-edge science and differentiation

Initially, McCormack’s relational searches reveal previously-unknown relationships which suggest that buprenorphine is a candidate for facilitated-internalization within a neurone, and that internalized buprenorphine targets the cytoplasmic (intracellular) aspect of non-opioid membrane-bound receptors, notably the NMDA receptor. This initial finding was followed by further new teachings which suggested that following binding to the mu opioid receptor the buprenorphine-mediated analgesic signal is transduced along pathways that differentiate this opioid from other opioids such as morphine. From these seminal findings it became clear that new systematic clinical evaluation of buprenorphine’s role in managing neuropathic pain was warranted. Subsequently, several studies confirmed the early outcomes of McCormack’s relational searches whereby some effects of buprenorphine are mediated by the NMDA receptor, both directly and indirectly.

Clinical implications of new teachings

Further probing and analysis by McCormack revealed that internalization of buprenorphine may be facilitated by ultra-low dose naloxone at a ratio of 20:1. Animal and clinical studies confirmed these findings and new patents were awarded (US 7,402,591; 6,995,161) for the potentiation of buprenorphine analgesia by ultra-low dose naloxone.

An elderly man in a wheelchair sits with a nurse in a red smock
© Shutterstock

Key outcomes

  • Expansion of use with new IP within an approved indication

Formal presentations of new teachings by Keith McCormack

  • Experimental indices used to classify opioids as partial or full receptor agonists may have limited clinical utility. Poster presentation at the 8th World Congress on Pain, Vancouver BC, Canada, 17th – 22nd August, 1996 (McCormack K, Brune K, Budd K, Prather P)
  • How far does functional promiscuity amongst receptor subtypes and G proteins explain diversity in clinical effects and interactions? Poster presentation at the 8th World Congress on Pain,Vancouver BC, Canada, 17th – 22nd August, 1996 (Prather P, Brune K, Budd K, McCormack K)
  • New Perspectives on Neuropathic Pain and Opioids. Society for Medicines Research, Controlling Pain in the 21st Century Symposium, Thursday 10th July 1997, Charing Cross & Westminster Medical School, London, United Kingdom.

Published new teachings

  • McCormack K. ‘Some new insights into the pharmacology of nonsteroidal anti-inflammatory drugs’. In: Novel Aspects of Pain Management: Opioids and Beyond, Sawynok J and Cowan A (Eds), John Wiley & Sons, New York. 1999, pp. 73-94.
  • McCormack K, Prather P, Chapleo C. ‘Some new insights into the effects of opioids in phasic and tonic nociceptive tests’. Pain 1998 78(2) 79-98.
  • McCormack K. ‘Signal transduction in neuropathic pain with special emphasis upon the analgesic role of opioids. Part I. The basic science of phenotype expression in the normal nerve and the regenerating nerve’. Pain Reviews 1999 6(1) 3-34.
  • McCormack K. ‘Signal transduction in neuropathic pain with special emphasis upon the analgesic role of opioids. Part II. Moving basic science toward a new pharmacotherapy’. Pain Reviews 1999 6(2) 99-131.
  • McCormack K. ‘A new perspective on signal transduction in neuropathic pain. The emerging role of the G protein beta gamma dimer in transducing and modulating opioid signaling’. In: Pain - Current Understanding, Emerging Therapies and Novel Approaches to Drug Therapy Eds. Munglani, Schmidt and Bountra, Taylor & Francis 2003 pp71-86.
  • McCormack K. ‘Fail-safe mechanisms that perpetuate neuropathic pain’. PAIN: Clinical Updates. Volume VII No. 3, Fall 1999.

Prior to filing of the patent application these new teachings were not made known within the public domain.