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European Biopharmaceutical Review

New Frontiers for Opioid Drugs

Although the psychological effects of opium were probably known to the ancient Babylonians over 6,000 years ago, it is welldocumented that extracts of the opium poppy Papaver somniferum have been used since the 3rd century BC to relieve pain, promote sleep and induce euphoria. Yet the use of opiates to treat diarrhoea and dysentery, perhaps surprisingly, appears to predate its other therapeutic applications, highlighting the important role of opioid signalling in the gastrointestinal (GI) system. In recent years, interest in the GI effects of opioids has been reignited by the development of selective agonists and antagonists and improved delivery methods that target opioid receptors in the GI system.

Crude opium contains more than 20 alkaloids. The main alkaloid constituent of opium, subsequently shown to be almost entirely responsible for the analgesic action, was isolated by Serturner in 1803 and given the name morphia, after Morpheus, the Greek god of dreams. In the intervening 200 years, our understanding of how opioid drugs work and their therapeutic potential has developed enormously.

This was primarily due to our current knowledge of the physiological and pathophysiological roles of opioid receptors, a great deal of which has arisen from in vitro pharmacology experiments using mammalian tissues. For the foreseeable future, opioid drugs will be important analgesics and anti-motility agents. However, other therapeutic uses are emerging as we begin to understand how opioid receptors influence sensation, inflammation, growth, secretion and absorption within the GI tract.

OPIOID RECEPTORS IN THE GASTROINTESTINAL TRACT

It is now well-established that there are three ‘classical’ types of opioid receptor, mu-, delta- and kappa-, and the genes encoding these receptors have been cloned. In 1994, cDNA encoding a fourth opioid receptor was identified...

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David Bunton is co-founder and Chief Operating Officer of Biopta Ltd, a human tissue based CRO that specialises in functional assays in ex vivo human tissues. David has a PhD in pharmacology, over eight years’ experience of preclinical contract research and developed the PM-1 instrument for the study of isolated tissues. Prior to founding Biopta, David was a Lecturer in Physiology at Glasgow Caledonian University.

Lee Rankin is a Study Director at Biopta Ltd. Lee has a Masters in Pharmacology from the University of Glasgow and has over five years’ experience of in vitro assays using human gastrointestinal tissues to study the effects of a range of drugs, in particular opioids.

Alistair Corbett is a Senior Lecturer at Glasgow Caledonian University, where his research focuses on the role of endogenous opioid peptides in intestinal disorders. Following his PhD at the University of Glasgow, Alistair joined Professor Hans Kosterlitz (codiscoverer of the enkephalins, the first endogenous opioid peptides) at the University of Aberdeen, producing more than 30 full publications and many conference presentations on various aspects of opioid physiology, pharmacology and chemistry.

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David Bunton
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Lee Rankin
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Alistair Corbett
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