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The Cholecystokinin Antagonist Proglumide Enhances the Analgesic Effect of Dihydrocodeine

McCleane, Gary J. MD

Clinical Journal of Pain:
Short Report

Aim: To investigate the potential pro-analgesic effect of the non-specific CCK antagonist proglumide on the analgesia produced by dihydrocodeine.

Method: A double-blind, placebo-controlled crossover study of 30 adult subjects.

Results: Mean pain scores fell from a baseline of 8.12–7.89 during the placebo phase (N.S.) and to 6.82 during the proglumide phase (P < 0.05). Side effects were minor.

Conclusion: The CCK antagonist proglumide enhances the analgesic effect of dihydrocodeine.

We have previously shown that the cholecystokinin (CCK) antagonist proglumide enhances the analgesic effect of sustained-release morphine in subjects with chronic pain of mixed etiology. 1 This peptide, represented in the central nervous system as well as the gut, 2 has an anti-opioid effect. 3 Levels of this peptide are increased after neural injury 4,5 and with chronic opiate administration. 6 Antagonism of these elevated levels in the animal model can enhance the analgesic effect of opiates. 7,8 The aim of this study was to examine if a CCK antagonist can enhance the analgesic effect of dihydrocodeine in human subjects.

Author Information

Rampark Pain Centre, Lurgan, Northern Ireland, United Kingdom

Received December 12, 2001; accepted March 10, 2003.

Reprints: Gary J. McCleane, Rampark Pain Centre, 2 Dromore Road, Lurgan, Northern Ireland, United Kingdom. E-mail:

© 2003 Lippincott Williams & Wilkins, Inc.