The Cholecystokinin Antagonist Proglumide Enhances the Analgesic Effect of Dihydrocodeine

  title={The Cholecystokinin Antagonist Proglumide Enhances the Analgesic Effect of Dihydrocodeine},
  author={Gary J. McCleane},
  journal={The Clinical Journal of Pain},
  • G. McCleane
  • Published 1 May 2003
  • Medicine, Biology, Chemistry, Psychology
  • The Clinical Journal of Pain
AimTo investigate the potential pro-analgesic effect of the non-specific CCK antagonist proglumide on the analgesia produced by dihydrocodeine. MethodA double-blind, placebo-controlled crossover study of 30 adult subjects. ResultsMean 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. ConclusionThe CCK antagonist proglumide enhances the analgesic effect of dihydrocodeine. 

Lack of Analgesic Synergy of the Cholecystokinin Receptor Antagonist Proglumide and Spinal Cord Stimulation for the Treatment of Neuropathic Pain in Rats

This work hypothesized that the analgesic effect of SCS would be enhanced through co‐administration with proglumide in animals with neuropathic pain, and reported that both systemic and spinal administration of proglums enhances analgesia produced by both low‐ and high‐frequency transcutaneous electrical nerve stimulation (TENS).

Cholecystokinin antagonists: can they augment opioid-derived analgesia?

  • G. McCleane
  • Biology, Psychology
    Journal of opioid management
  • 2005
The initial findings from human studies confirm the strong impression from the animal literature that CCK has an integral part in nociceptive processing and that antagonists of its action have a useful proanalgesic effect.

Enhanced antinociceptive effects of mitragynine in combination with morphine via opioid receptors activation

The combination of MG and morphine has enhanced morphine-induced analgesia which shows synergism in analgesic action and the effect on the development of tolerance due to morphine acutely and chronically is investigated.


Known and hypothesized pathophysiologic mechanisms surounding opioid tolerance and opioid-induced hyperalgesia are viewed, including complex intracellular neural mechnisms, and the clinical implications for pain are outlined.

Pharmacological strategies in relieving neuropathic pain

  • G. McCleane
  • Medicine
    Expert opinion on pharmacotherapy
  • 2004
A number of drugs currently licensed for a different indication have recently had an analgesic effect in neuropathic pain attributed to them and a number of novel compounds are undergoing investigation and provide hope of dicovering more efficacious treatment options in the future.

Mechanisms of opioid-induced tolerance and hyperalgesia.

  • A. DuPenDanny D. ShenM. Ersek
  • Medicine, Psychology
    Pain management nursing : official journal of the American Society of Pain Management Nurses
  • 2007

Strategies to reduce morphine tolerance in cancer : evaluation of the bifunctional opioid UFP-505

An extensive pharmacological in vitro and in vivo characterization is made and a MOPagonist/DOP-partial agonist is shown to produce strong antinociception with no tolerance; further work on bifunctional opioids may lead to a better understanding of the mechanisms of analgesic tolerance.

Cholecystokinin Drives Descending Facilitation to Mediate Morphine-Induced Paradoxical "Pain" and Antinociceptive Tolerance

Cholecystokinin in the Rostral Ventromedial Medulla Drives Descending Facilitation to Mediate Morphineinduced Paradoxical Pain and Spinal Antinociceptive Tolerance.

Novel Pharmacological Nonopioid Therapies in Chronic Pain

The pharmacotherapies discussed in this manuscript outline promising opioid alternatives which can change the future of chronic pain treatment.



The Cholecystokinin Antagonist Proglumide Enhances the Analgesic Efficacy of Morphine in Humans with Chronic Benign Pain

  • G. McCleane
  • Medicine, Biology
    Anesthesia and analgesia
  • 1998
It is demonstrated that the cholecystokinin antagonist proglumide increases the analgesic effect of morphine in some patients with chronic benign pain.

Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia.

A physiological role for cholecystokinin as a specific opiate antagonist in analgesia-mediating systems is suggested and a similar mode of action may explain other behavioral effects of chole CyStokinin, such as suppression of food intake.

Potentiation of morphine analgesia by the cholecystokinin antagonist proglumide

Regulation of morphine antiallodynic efficacy by cholecystokinin in a model of neuropathic pain in rats.

The finding that DAMGO, but not very large doses of morphine, produced antiallodynic actions suggests that the ability of mu opioids to alleviate the allodynia is related, in part, to efficacy at postsynaptic mu receptors.

The Effects of Intrathecally Administered FK480, a Cholecystokinin-A Receptor Antagonist, and YM022, a Cholecystokinin-B Receptor Antagonist, on the Formalin Test in the Rat

Data indicate that aCCK-B receptor antagonist, but not a CCK-A receptor antagonists, produces an antinociceptive effect in the rat formalin test, and this effect was not mediated by the spinal opioid receptor activation.

The CCK-B receptor antagonist Cl 988 reverses tolerance to morphine in rats.

The results suggest that upregulation of the endogenous CCK system during repeated morphine administration may have an important role in the development of opiate tolerance.