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December 2007 Issue
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Strong drugs without the addiction


Two University of Adelaide pharmacologists working with one the world's leading neuroscientists have helped pave the way for the development of new pain-killing drugs that are not addictive.

Professor of Clinical Pharmacology at the University of Adelaide Paul Rolan and postdoctoral fellow Dr Mark Hutchinson are part of a combined US and Australian research team that has made a breakthrough in revealing how opioid drugs such as morphine both relieve pain and also cause addiction.

The Adelaide scientists and senior colleagues at the University of Colorado, including world glia and pain expert Dr Linda Watkins, have isolated in animal models the effect that morphine has on the brain's immune cells, known as glia, and also on nerve cells (neurons).

Glial cells heighten nerve pain such as sciatica by exciting the neurons that transmit pain signals. While morphine deadens pain by acting at nerve synapses, it also activates glial cells, worsening the drug's side effects, such as drowsiness, tolerance and addiction.

The scientists tested a new drug called AV411 that blocks morphine's effects on glia but not on neurons, resulting in effective pain relief without the side effects of addiction. AV411 is being developed by Avigen Inc., a Californian biopharmaceutical company.

Vice President of Research & Development at Avigen Dr Kirk Johnson said the company was working in collaboration with Dr Hutchinson, Dr Watkins and Professor Rolan.

"Currently, AV411 is in clinical trials at the Royal Adelaide Hospital for neuropathic pain and we look forward to exploring this molecule in opioid withdrawal," Dr Johnson said.

"Doctors prescribe morphine for pain relief but opioids come with the potential for addiction or abuse," Dr Hutchinson said.

"Our tests show that by blocking morphine's effects on glial cells, it stops cravings for the drug."

These pre-clinical findings were reported last month at the annual meeting of the Society for Neuro-science, the world's largest organisation of scientists devoted to the study of the brain. The prestigious international journal Science also published the findings last month.

The Director of the National Institute on Drug Abuse in the United States, Dr Nora Volkow, said the research helped to "pave the way toward developing new, potent, non-addictive medications".

Dr Hutchinson graduated with a Bachelor of Science degree with First Class Honours from the University of Adelaide in 1999, majoring in microbiology, immunology and pharmacology. In 2005 he was awarded an American-Australian Association Fellowship and has been working with Dr Watkins in Colorado for the past three years.

He is now a NHMRC CJ Martin Postdoctoral Fellow, which will enable him to return to the University of Adelaide to continue working with his colleagues in the Discipline of Pharmacology.

In November, Professor Rolan addressed the 10th International Conference on the Mechanisms and Treatment of Neuropathic Pain held in Salt Lake City, Utah. He told delegates that summary data showed that AV411 was "a promising non-opioid clinical candidate for chronic neuropathic pain".

The other US scientists involved in the research include Dr Steven Maier from the Department of Psychology and Centre for Neuroscience at the University of Colorado and postdoctoral fellow Sondra Blond.

Story by Candy Gibson

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Left: Professor Paul Rolan, from the University’s Discipline of Clinical & Experimental Pharmacology, at the Royal Adelaide Hospital
Photo by Candy Gibson

Left: Professor Paul Rolan, from the University's Discipline of Clinical & Experimental Pharmacology, at the Royal Adelaide Hospital
Photo by Candy Gibson

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