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Proglumide

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Proglumide (Milid) is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist,[1] which blocks both the CCKA and CCKB subtypes.[2] It was used mainly in the treatment of stomach ulcers,[3][4] although it has now been largely replaced by newer drugs for this application.

An interesting side effect of proglumide is that it enhances the analgesia produced by opioid drugs,[5] and can prevent or even reverse the development of tolerance to opioid drugs.[6][7] This can make it a useful adjuvant treatment to use alongside opioid drugs in the treatment of chronic pain conditions such as cancer, where opioid analgesics may be required for long periods and development of tolerance reduces clinical efficacy of these drugs.[8][9]

Proglumide has also been shown to act as a δ-opioid agonist, which may contribute to its analgesic effects.[10]

Proglumide also works as a placebo effect amplifier for pain conditions. When injected visibly to a subject, its analgesic effect is bigger than a similarly administered placebo. When injected secretly, it does not have any effect, whereas standard pain drugs have an effect, even if they are administered without the subject's awareness.[11] The supposed mechanism is an enhancement of the neural pathways of expectation.

See also Edit

References Edit

  1. (1985). Further studies on the specificity of proglumide as a selective cholecystokinin antagonist in the central nervous system. Annals of the New York Academy of Sciences 448: 345–51.
  2. (2005). Selective CCK-A but not CCK-B receptor antagonists inhibit HT-29 cell proliferation: Synergism with pharmacological levels of melatonin. Journal of Pineal Research 39 (3): 243–50.
  3. (1981). Duodenal ulcer - multicenter double-blind study with proglumide. Medizinische Klinik 76 (8): 226–9.
  4. (1987). Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats. The Journal of Pharmacology and Experimental Therapeutics 241 (2): 602–7.
  5. (2003). The cholecystokinin antagonist proglumide enhances the analgesic effect of dihydrocodeine. The Clinical journal of pain 19 (3): 200–1.
  6. (1984). Potentiation of opiate analgesia and apparent reversal of morphine tolerance by proglumide. Science 224 (4647): 395–6.
  7. (1984). Proglumide prevents and curtails acute tolerance to morphine in rats. Neuropharmacology 23 (6): 715–8.
  8. (1998). Proglumide as a morphine adjunct in cancer pain management. Journal of pain and symptom management 15 (5): 314–20.
  9. (1998). The cholecystokinin antagonist proglumide enhances the analgesic efficacy of morphine in humans with chronic benign pain. Anesthesia and Analgesia 87 (5): 1117–20.
  10. (1987). Proglumide exhibits delta opioid agonist properties. Alcohol and drug research 7 (3): 135–46.
  11. (1995). Potentiation of placebo analgesia by proglumide. Lancet 346 (8984): 1231.


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