Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H26N2O4 |
Molecular Weight | 334.4107 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCN(CCC)C(=O)C(CCC(=O)O)N=C(c1ccccc1)O
InChI
InChIKey=DGMKFQYCZXERLX-UHFFFAOYSA-N
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)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/2862828Curator's Comment:: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/2299627 | https://www.ncbi.nlm.nih.gov/pubmed/2741440 | https://www.drugs.com/international/proglumide.html | https://goo.gl/d51Yn7 | https://www.ncbi.nlm.nih.gov/pubmed/3651819 | https://www.ncbi.nlm.nih.gov/pubmed/2994583
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2862828
Curator's Comment:: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/2299627 | https://www.ncbi.nlm.nih.gov/pubmed/2741440 | https://www.drugs.com/international/proglumide.html | https://goo.gl/d51Yn7 | https://www.ncbi.nlm.nih.gov/pubmed/3651819 | https://www.ncbi.nlm.nih.gov/pubmed/2994583
Proglumide is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist, which blocks both the CCKA and CCKB subtypes. It was used mainly in the treatment of stomach ulcers, 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, and can prevent or even reverse the development of tolerance to opioid drugs. 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.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2299627 |
250.0 µM [IC50] | ||
Target ID: CHEMBL298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2299627 |
900.0 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Proglumide Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Opioidergic effects of nonopioid analgesics on the central nervous system. | 2002 Dec |
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Pharmacological effects of oxytocin on gastric emptying and intestinal transit of a non-nutritive liquid meal in female rats. | 2003 Apr |
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Enterostatin inhibition of dietary fat intake is dependent on CCK-A receptors. | 2003 Aug |
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CCK-1 receptor blockade for treatment of biliary colic: a pilot study. | 2003 Aug 1 |
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Effect of cholecystokinin1 receptor antagonist loxiglumide (CR1505) on basal pancreatic exocrine secretion in conscious rats. | 2003 Jan |
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Involvement of local cholecystokinin in the tolerance induced by morphine microinjections into the periaqueductal gray of rats. | 2003 Mar |
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Role for the cholecystokinin-A receptor in fever: a study of a mutant rat strain and a pharmacological analysis. | 2003 Mar 15 |
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Effect of Dai-kenchu-to (Da-Jian-Zhong-Tang) on the delayed intestinal propulsion induced by chlorpromazine in mice. | 2003 May |
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Role of leptin in the control of feeding of goldfish Carassius auratus: interactions with cholecystokinin, neuropeptide Y and orexin A, and modulation by fasting. | 2003 May 16 |
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Differential mechanism and site of action of CCK on the pancreatic secretion and growth in rats. | 2003 Oct |
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The effects of an essential fatty acid compound and a cholecystokinin-8 antagonist on iron deficiency induced anorexia and learning deficits. | 2004 Apr |
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Sensitive SPE-HPLC method to determine a novel angiotensin-AT1 antagonist in biological samples. | 2004 Apr 16 |
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Suppression of food intake by GI fatty acid infusions: roles of celiac vagal afferents and cholecystokinin. | 2004 Aug |
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Glycine-extended gastrin induces matrix metalloproteinase-1- and -3-mediated invasion of human colon cancer cells through type I collagen gel and Matrigel. | 2004 Aug 10 |
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Effects of juice from Morinda citrifolia (Noni) on gastric emptying in male rats. | 2004 Dec 31 |
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Cholecystokinin octapeptide increases free intracellular calcium of guinea pig cardiomyocytes through activation of Ca2+ channel and tyrosine kinase. | 2004 Feb 25 |
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Cholecystokinin octapeptide inhibits carotid sinus baroreflex in anesthetized rats. | 2004 Feb 25 |
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Anxiogenic effect of cholecystokinin in the dorsal periaqueductal gray. | 2004 Jan |
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Involvement of capsaicin-sensitive afferent nerves and cholecystokinin 2/gastrin receptors in gastroprotection and adaptation of gastric mucosa to Helicobacter pylori-lipopolysaccharide. | 2004 Jul |
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Differential contribution of cholecystokinin receptors to stress-induced modulation of seizure and nociception thresholds in mice. | 2004 Jun |
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Long-term bile diversion enhances basal and duodenal oleate-stimulated pancreatic exocrine secretion in dogs. | 2004 Jun |
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Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. | 2004 Mar 17 |
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[New aspects of pharmaco-therapy for acute pancreatitis]. | 2004 Nov |
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Involvement of cholecystokinin in the opioid tolerance induced by dipyrone (metamizol) microinjections into the periaqueductal gray matter of rats. | 2004 Nov |
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Use of a hepta-Tyr antibiotic modified silica stationary phase for the enantiomeric resolution of D,L-loxiglumide by electrochromatography and nano-liquid chromatography. | 2004 Oct 8 |
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Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids. | 2005 Apr 6 |
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Proglumide attenuates experimental colitis in rats. | 2005 Mar |
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Long-term effects of proglumide on resection of cardiac adenocarcinoma. | 2005 May 7 |
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Role of cholecystokinin in appetite control and body weight regulation. | 2005 Nov |
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The combined effects of proglumide and fluorouracil on the growth of murine Colon 38 cancer cells in vitro. | 2005 Nov-Dec |
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Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity. | 2005 Sep |
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CCK1 antagonists: are they ready for clinical use? | 2006 |
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Anthranilic acid based CCK1 receptor antagonists and CCK-8 have a common step in their "receptor desmodynamic processes". | 2006 Apr 20 |
|
Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors. | 2006 Feb |
|
[Effects of gastrin receptor antagonist and cyclooxygenase-2 inhibitor on proliferation and apoptosis of gastric cancer cell]. | 2006 Jan 24 |
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Effects of the cholecystokinin A receptor antagonist loxiglumide on the proliferation and cell cycle time of pancreatic acinar cells in rats. | 2006 Mar |
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[Receptor mechanisms underlying the modulation of lipopolysaccharide-induced nuclear factor-kappaB expression in vascular endothelial cells by cholecystokinin octapeptide]. | 2006 Mar |
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Naloxone, not proglumide or MK-801, alters effects of morphine preexposure on morphine-induced taste aversions. | 2006 May |
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Cholecystokinin hyperresponsiveness in functional dyspepsia. | 2006 May 7 |
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Gastrin induces leukocyte-endothelial cell interactions in vivo and contributes to the inflammation caused by Helicobacter pylori. | 2006 Nov |
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Cholecystokinin-8s excites identified rat pancreatic-projecting vagal motoneurons. | 2007 Aug |
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Vagally mediated, nonparacrine effects of cholecystokinin-8s on rat pancreatic exocrine secretion. | 2007 Aug |
|
Estrogen receptor alpha-induced cholecystokinin type A receptor expression in the female mouse pituitary. | 2007 Dec |
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The inhibitory effect of proglumide on meal-induced insulin sensitization in rats. | 2007 Jul |
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Activation of spinal cholecystokinin and neurokinin-1 receptors is associated with the attenuation of intrathecal morphine analgesia following electroacupuncture stimulation in rats. | 2007 Jun |
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The use of animal models to study bacterial translocation during acute pancreatitis. | 2007 May |
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Effect of intravenous infusion of proglumide on ruminal motility in conscious sheep (Ovis aries). | 2007 Nov |
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Gastric antisecretory drugs induce leukocyte-endothelial cell interactions through gastrin release and activation of CCK-2 receptors. | 2007 Oct |
|
Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake. | 2007 Oct |
|
The effect of luminal ghrelin on pancreatic enzyme secretion in the rat. | 2007 Oct 4 |
Patents
Sample Use Guides
PO 400 mg 2-4 times/day, up to 800 mg 3 times/day. IV/IM 400-800 mg/day.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2994583
The cell lines SW 403, Ls 174 T and Lovo (provided by the Institute for Immunbiology, Freiburg) were cultured in Dulbecco's or RPMI medium, with 10% fetal calf serum and antibiotics. The effects of proglumide (Milid, Opfermann, Bergisch-Gladbach) were estimated by cell count (Neubauer) and measurement of incorporation of [3H]thymidine (Amersham-Buchler, Braunschweig). Cells were counted after trypsinization (0.03%, 37 ~ C, 30rain in Hank's EDTA, Gibco) at the second and eighth day of culture. After cell harvesting, [3H]thymidine incorporation was estimated by beta counting equipment. Six-well plates containing 4 x 104 cells were used in each cellcounting experiment; 96-well plates were used for each [3H]thymidine-incorporation experiment. Medium was changed every second day and cell viability was proved by eosin staining. Gastrin and CEA concentrations were estimated by radioimmunoassay (Travenol, M/inchen; Abbott, Wiesbaden) in cell-culture medium. For synchronization the cells were incubated for 48 h in Dulbecco's or RPMI medium without fetal calf serum (37 ~ C). The cells were then cooled to 4 ~ C for 24 h and fetal calf serum (10%) and thymidine (2 nmol) were added. About 70%-75% cells survived this procedure, as has been shown by eosin staining. After 24 h the cells were incubated with various concentrations of gastrin, pentagastrin or proglumide.
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Classification Tree | Code System | Code | ||
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WHO-ATC |
A02BX06
Created by
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NCI_THESAURUS |
C28197
Created by
admin on Fri Jun 25 22:03:45 UTC 2021 , Edited by admin on Fri Jun 25 22:03:45 UTC 2021
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FDA ORPHAN DRUG |
762120
Created by
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FDA ORPHAN DRUG |
743020
Created by
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FDA ORPHAN DRUG |
756620
Created by
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WHO-VATC |
QA02BX06
Created by
admin on Fri Jun 25 22:03:45 UTC 2021 , Edited by admin on Fri Jun 25 22:03:45 UTC 2021
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NCI_THESAURUS |
C29701
Created by
admin on Fri Jun 25 22:03:45 UTC 2021 , Edited by admin on Fri Jun 25 22:03:45 UTC 2021
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Code System | Code | Type | Description | ||
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EPL8W5565D
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PRIMARY | |||
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4922
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PRIMARY | |||
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C81916
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PRIMARY | |||
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25727-74-6
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SUPERSEDED | |||
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2281
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PRIMARY | |||
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PROGLUMIDE
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8730
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PRIMARY | RxNorm | ||
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6620-60-6
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CHEMBL316561
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2161
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PRIMARY | |||
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M9161
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PRIMARY | Merck Index | ||
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229-567-4
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PRIMARY | |||
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D011377
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PRIMARY | |||
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DB13431
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24485-90-3
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6620-60-6
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admin on Fri Jun 25 22:03:45 UTC 2021 , Edited by admin on Fri Jun 25 22:03:45 UTC 2021
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PRIMARY | |||
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SUB10078MIG
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PRIMARY |
ACTIVE MOIETY