Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C18H26N2O4 |
| Molecular Weight | 334.41 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCN(CCC)C(=O)C(CCC(O)=O)NC(=O)C1=CC=CC=C1
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)
| Molecular Formula | C18H26N2O4 |
| Molecular Weight | 334.41 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
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 |
|---|---|---|---|---|
| Primary | Proglumide Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7847 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
9721 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
10635 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
43300 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
30400 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
31800 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/35336003/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROGLUMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 9.0 |
inconclusive | |||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
Page: 344.0 |
no | |||
Page: 372.0 |
no | |||
Sources: https://edoc.unibas.ch/84877/ |
no | |||
| yes [Inhibition 10 uM] | ||||
| yes [Inhibition 10 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 371 | 374 |
no |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Estrogen receptor alpha-induced cholecystokinin type A receptor expression in the female mouse pituitary. | 2007-12 |
|
| Effect of intravenous infusion of proglumide on ruminal motility in conscious sheep (Ovis aries). | 2007-11 |
|
| The effect of luminal ghrelin on pancreatic enzyme secretion in the rat. | 2007-10-04 |
|
| Gastric antisecretory drugs induce leukocyte-endothelial cell interactions through gastrin release and activation of CCK-2 receptors. | 2007-10 |
|
| Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake. | 2007-10 |
|
| Cholecystokinin-8s excites identified rat pancreatic-projecting vagal motoneurons. | 2007-08 |
|
| Vagally mediated, nonparacrine effects of cholecystokinin-8s on rat pancreatic exocrine secretion. | 2007-08 |
|
| The inhibitory effect of proglumide on meal-induced insulin sensitization in rats. | 2007-07 |
|
| Activation of spinal cholecystokinin and neurokinin-1 receptors is associated with the attenuation of intrathecal morphine analgesia following electroacupuncture stimulation in rats. | 2007-06 |
|
| The use of animal models to study bacterial translocation during acute pancreatitis. | 2007-05 |
|
| Enterostatin (APGPR) enhances memory consolidation in mice. | 2007-03 |
|
| Peripheral participation of cholecystokinin in the morphine-induced peripheral antinociceptive effect in non-diabetic and diabetic rats. | 2007-03 |
|
| Mechanism of the induction of brain c-Fos-positive neurons by lipid absorption. | 2007-01 |
|
| The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. | 2006-11-15 |
|
| Gastrin induces leukocyte-endothelial cell interactions in vivo and contributes to the inflammation caused by Helicobacter pylori. | 2006-11 |
|
| Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen. | 2006-10-27 |
|
| The combined effects of proglumide and fluorouracil on the growth of murine Colon 38 cancer cells in vitro. | 2006-07-06 |
|
| Caerulein-induced acute pancreatitis in mice that constitutively overexpress Reg/PAP genes. | 2006-05-15 |
|
| Cholecystokinin hyperresponsiveness in functional dyspepsia. | 2006-05-07 |
|
| Naloxone, not proglumide or MK-801, alters effects of morphine preexposure on morphine-induced taste aversions. | 2006-05 |
|
| Involvement of cholecystokinin in peripheral nociceptive sensitization during diabetes in rats as revealed by the formalin response. | 2006-05 |
|
| Anthranilic acid based CCK1 receptor antagonists and CCK-8 have a common step in their "receptor desmodynamic processes". | 2006-04-20 |
|
| Effects of the cholecystokinin A receptor antagonist loxiglumide on the proliferation and cell cycle time of pancreatic acinar cells in rats. | 2006-03 |
|
| [Receptor mechanisms underlying the modulation of lipopolysaccharide-induced nuclear factor-kappaB expression in vascular endothelial cells by cholecystokinin octapeptide]. | 2006-03 |
|
| Estrogen and CCK1 receptor modification of mu-opioid receptor binding in the cortex of female rats. | 2006-02-16 |
|
| Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors. | 2006-02 |
|
| [Effects of gastrin receptor antagonist and cyclooxygenase-2 inhibitor on proliferation and apoptosis of gastric cancer cell]. | 2006-01-24 |
|
| Effects of amylin on feeding of goldfish: interactions with CCK. | 2006-01-15 |
|
| CCK1 antagonists: are they ready for clinical use? | 2006 |
|
| Effect of cholecystokinin octapeptide on diacylglycerol-PKC signaling pathway in rat pulmonary interstitial macrophages stimulated by lipopolysaccharide. | 2005-12 |
|
| Role of cholecystokinin in appetite control and body weight regulation. | 2005-11 |
|
| Selective CCK-A but not CCK-B receptor antagonists inhibit HT-29 cell proliferation: synergism with pharmacological levels of melatonin. | 2005-10 |
|
| Cholecystokinin octapeptide increases spontaneous glutamatergic synaptic transmission to neurons of the nucleus tractus solitarius centralis. | 2005-10 |
|
| Cholecystokinin1 receptors mediate the increase in Fos-like immunoreactivity in the rat myenteric plexus following intestinal oleate infusion. | 2005-09-15 |
|
| Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity. | 2005-09 |
|
| Cholecystokinin octapeptide improves cardiac function by activating cholecystokinin octapeptide receptor in endotoxic shock rats. | 2005-06-14 |
|
| Long-term effects of proglumide on resection of cardiac adenocarcinoma. | 2005-05-07 |
|
| Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids. | 2005-04-06 |
|
| Proglumide attenuates experimental colitis in rats. | 2005-03 |
|
| Cholecystokinin inhibits evoked inhibitory postsynaptic currents in the rat nucleus accumbens indirectly through gamma-aminobutyric acid and gamma-aminobutyric acid type B receptors. | 2005-02-01 |
|
| Effects of juice from Morinda citrifolia (Noni) on gastric emptying in male rats. | 2004-12-31 |
|
| [New aspects of pharmaco-therapy for acute pancreatitis]. | 2004-11 |
|
| Involvement of cholecystokinin in the opioid tolerance induced by dipyrone (metamizol) microinjections into the periaqueductal gray matter of rats. | 2004-11 |
|
| Use of a hepta-Tyr antibiotic modified silica stationary phase for the enantiomeric resolution of D,L-loxiglumide by electrochromatography and nano-liquid chromatography. | 2004-10-08 |
|
| Effect of lipopolysaccharide on expression and characterization of cholecystokinin receptors in rat pulmonary interstitial macrophages. | 2004-10 |
|
| Pharmacological study of IQM-97,423, a potent and selective CCK1 receptor antagonist with protective effect in experimental acute pancreatitis. | 2004-10 |
|
| Cholecystokinin-induced satiety is mediated through interdependent cooperation of CCK-A and 5-HT3 receptors. | 2004-09-30 |
|
| Suppression of food intake by GI fatty acid infusions: roles of celiac vagal afferents and cholecystokinin. | 2004-08 |
|
| Differential contribution of cholecystokinin receptors to stress-induced modulation of seizure and nociception thresholds in mice. | 2004-06 |
|
| The effects of an essential fatty acid compound and a cholecystokinin-8 antagonist on iron deficiency induced anorexia and learning deficits. | 2004-04 |
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.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Apr 02 09:53:23 GMT 2025
by
admin
on
Wed Apr 02 09:53:23 GMT 2025
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| Record UNII |
EPL8W5565D
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| Record Status |
Validated (UNII)
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WHO-ATC |
A02BX06
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NCI_THESAURUS |
C28197
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FDA ORPHAN DRUG |
762120
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FDA ORPHAN DRUG |
743020
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FDA ORPHAN DRUG |
756620
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WHO-VATC |
QA02BX06
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NCI_THESAURUS |
C29701
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EPL8W5565D
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757841
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C81916
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25727-74-6
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2281
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PROGLUMIDE
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8730
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DTXSID7023516
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CHEMBL316561
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2161
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m9161
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229-567-4
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D011377
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DB13431
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24485-90-3
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6620-60-6
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SUB10078MIG
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100000081122
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ACTIVE MOIETY |
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