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 receptor (DOR) agonist, which may contribute to its analgesic effects.[10] However, other studies show that proglumide has low affinity to the μ-opioid receptor (MOR) and the κ-opioid receptor (KOR) (13% of MOR and 17% of KOR occupancy at 100 μM), but no affinity to DOR.[11] It is questionable whether this is clinically significant, since the concentration they used was very high, and the occupancies were low even at that point.
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.[12] The supposed mechanism is an enhancement of the neural pathways of expectation as a result of dopamine and endogenous opioids being suddenly released throughout numerous structures of the brain and spinal cord.
The ventral tegmental area is the structure believed to mediate proglumide's analgesic and euphoric effects, however dozens of areas with a wide range of physical and psychological functions are implicated in the mediation of the placebo effect (this accounts for proglumide's ability to produce physically measurable effects on vital signs such as heart rate, blood pressure, respiration rate, and tidal volume which cannot be accounted for by its clinically insignificant δ-opioid affinity.
^Bunney BS, Chiodo LA, Freeman AS (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 (1): 345–351. Bibcode:1985NYASA.448..345B. doi:10.1111/j.1749-6632.1985.tb29929.x. PMID 2862828. S2CID 28298172.
^González-Puga C, García-Navarro A, Escames G, León J, López-Cantarero M, Ros E, Acuña-Castroviejo D (October 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): 243–250. doi:10.1111/j.1600-079X.2005.00239.x. PMID 16150104. S2CID 20187767.
^Bergemann W, Consentius K, Braun HE, Hirschmann H, Marowski B, Munck A, et al. (April 1981). "[Duodenal ulcer - multicenter double-blind study with proglumide]". Medizinische Klinik. 76 (8): 226–229. PMID 7231338.
^Tariq M, Parmar NS, Ageel AM (May 1987). "Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats". The Journal of Pharmacology and Experimental Therapeutics. 241 (2): 602–607. PMID 3572816.
^McCleane GJ (2003). "The cholecystokinin antagonist proglumide enhances the analgesic effect of dihydrocodeine". The Clinical Journal of Pain. 19 (3): 200–201. doi:10.1097/00002508-200305000-00008. PMID 12792559. S2CID 29229782.
^Watkins LR, Kinscheck IB, Mayer DJ (April 1984). "Potentiation of opiate analgesia and apparent reversal of morphine tolerance by proglumide". Science. 224 (4647): 395–396. Bibcode:1984Sci...224..395W. doi:10.1126/science.6546809. PMID 6546809.
^Tang J, Chou J, Iadarola M, Yang HY, Costa E (June 1984). "Proglumide prevents and curtails acute tolerance to morphine in rats". Neuropharmacology. 23 (6): 715–718. doi:10.1016/0028-3908(84)90171-0. PMID 6462377. S2CID 33168040.
^Bernstein ZP, Yucht S, Battista E, Lema M, Spaulding MB (May 1998). "Proglumide as a morphine adjunct in cancer pain management". Journal of Pain and Symptom Management. 15 (5): 314–320. doi:10.1016/s0885-3924(98)00003-7. PMID 9654837.
^McCleane GJ (November 1998). "The cholecystokinin antagonist proglumide enhances the analgesic efficacy of morphine in humans with chronic benign pain". Anesthesia and Analgesia. 87 (5): 1117–1120. doi:10.1213/00000539-199811000-00025. PMID 9806692. S2CID 10735834.
^Rezvani A, Stokes KB, Rhoads DL, Way EL (1987). "Proglumide exhibits delta opioid agonist properties". Alcohol and Drug Research. 7 (3): 135–146. PMID 3030338.
^Gaudreau P, Lavigne GJ, Quirion R (May 1990). "Cholecystokinin antagonists proglumide, lorglumide and benzotript, but not L-364,718, interact with brain opioid binding sites". Neuropeptides. 16 (1): 51–55. doi:10.1016/0143-4179(90)90029-X. PMID 2174522. S2CID 25646937.
^Benedetti F, Amanzio M, Maggi G (November 1995). "Potentiation of placebo analgesia by proglumide". Lancet. 346 (8984): 1231. doi:10.1016/S0140-6736(95)92938-X. PMID 7475687.
January 01, 1970
proglumide, milid, drug, that, inhibits, gastrointestinal, motility, reduces, gastric, secretions, acts, cholecystokinin, antagonist, which, blocks, both, ccka, cckb, subtypes, used, mainly, treatment, stomach, ulcers, although, been, largely, replaced, newer,. 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 ProglumideClinical dataOther names RS N2 benzoyl N N dipropyl a glutamineAHFS Drugs comInternational Drug NamesRoutes ofadministrationOralATC codeA02BX06 WHO Legal statusLegal statusIn general Prescription only Pharmacokinetic dataElimination half life 24 hoursIdentifiersIUPAC name 4 Benzamido 5 dipropylamino 5 oxopentanoic acidCAS Number6620 60 6 YPubChem CID4922IUPHAR BPS893ChemSpider4753 NUNIIEPL8W5565DChEBICHEBI 32058 NChEMBLChEMBL316561 NCompTox Dashboard EPA DTXSID7023516ECHA InfoCard100 026 880Chemical and physical dataFormulaC 18H 26N 2O 4Molar mass334 416 g mol 13D model JSmol Interactive imageSMILES CCCN CCC C O C CCC O O NC O c1ccccc1InChI InChI 1S C18H26N2O4 c1 3 12 20 13 4 2 18 24 15 10 11 16 21 22 19 17 23 14 8 6 5 7 9 14 h5 9 15H 3 4 10 13H2 1 2H3 H 19 23 H 21 22 NKey DGMKFQYCZXERLX UHFFFAOYSA N N N Y what is this verify 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 d opioid receptor DOR agonist which may contribute to its analgesic effects 10 However other studies show that proglumide has low affinity to the m opioid receptor MOR and the k opioid receptor KOR 13 of MOR and 17 of KOR occupancy at 100 mM but no affinity to DOR 11 It is questionable whether this is clinically significant since the concentration they used was very high and the occupancies were low even at that point 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 12 The supposed mechanism is an enhancement of the neural pathways of expectation as a result of dopamine and endogenous opioids being suddenly released throughout numerous structures of the brain and spinal cord The ventral tegmental area is the structure believed to mediate proglumide s analgesic and euphoric effects however dozens of areas with a wide range of physical and psychological functions are implicated in the mediation of the placebo effect this accounts for proglumide s ability to produce physically measurable effects on vital signs such as heart rate blood pressure respiration rate and tidal volume which cannot be accounted for by its clinically insignificant d opioid affinity See also editProglumetacinReferences edit Bunney BS Chiodo LA Freeman AS 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 1 345 351 Bibcode 1985NYASA 448 345B doi 10 1111 j 1749 6632 1985 tb29929 x PMID 2862828 S2CID 28298172 Gonzalez Puga C Garcia Navarro A Escames G Leon J Lopez Cantarero M Ros E Acuna Castroviejo D October 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 3 243 250 doi 10 1111 j 1600 079X 2005 00239 x PMID 16150104 S2CID 20187767 Bergemann W Consentius K Braun HE Hirschmann H Marowski B Munck A et al April 1981 Duodenal ulcer multicenter double blind study with proglumide Medizinische Klinik 76 8 226 229 PMID 7231338 Tariq M Parmar NS Ageel AM May 1987 Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats The Journal of Pharmacology and Experimental Therapeutics 241 2 602 607 PMID 3572816 McCleane GJ 2003 The cholecystokinin antagonist proglumide enhances the analgesic effect of dihydrocodeine The Clinical Journal of Pain 19 3 200 201 doi 10 1097 00002508 200305000 00008 PMID 12792559 S2CID 29229782 Watkins LR Kinscheck IB Mayer DJ April 1984 Potentiation of opiate analgesia and apparent reversal of morphine tolerance by proglumide Science 224 4647 395 396 Bibcode 1984Sci 224 395W doi 10 1126 science 6546809 PMID 6546809 Tang J Chou J Iadarola M Yang HY Costa E June 1984 Proglumide prevents and curtails acute tolerance to morphine in rats Neuropharmacology 23 6 715 718 doi 10 1016 0028 3908 84 90171 0 PMID 6462377 S2CID 33168040 Bernstein ZP Yucht S Battista E Lema M Spaulding MB May 1998 Proglumide as a morphine adjunct in cancer pain management Journal of Pain and Symptom Management 15 5 314 320 doi 10 1016 s0885 3924 98 00003 7 PMID 9654837 McCleane GJ November 1998 The cholecystokinin antagonist proglumide enhances the analgesic efficacy of morphine in humans with chronic benign pain Anesthesia and Analgesia 87 5 1117 1120 doi 10 1213 00000539 199811000 00025 PMID 9806692 S2CID 10735834 Rezvani A Stokes KB Rhoads DL Way EL 1987 Proglumide exhibits delta opioid agonist properties Alcohol and Drug Research 7 3 135 146 PMID 3030338 Gaudreau P Lavigne GJ Quirion R May 1990 Cholecystokinin antagonists proglumide lorglumide and benzotript but not L 364 718 interact with brain opioid binding sites Neuropeptides 16 1 51 55 doi 10 1016 0143 4179 90 90029 X PMID 2174522 S2CID 25646937 Benedetti F Amanzio M Maggi G November 1995 Potentiation of placebo analgesia by proglumide Lancet 346 8984 1231 doi 10 1016 S0140 6736 95 92938 X PMID 7475687 Retrieved from https en wikipedia org w index php title Proglumide amp oldid 1211381672, wikipedia, 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