U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of PROGLUMIDE

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)

HIDE SMILES / InChI

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 ( + / - )

Description
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.

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
250.0 µM [IC50]
900.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Proglumide

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7847 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
43300 ng × h/mL
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
3 h
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
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
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
Doses

Doses

DosePopulationAdverse events​
1200 mg 1 times / day multiple, oral
Studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
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]
no
no
no
yes [Inhibition 10 uM]
yes [Inhibition 10 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Tox targets
PubMed

PubMed

TitleDatePubMed
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

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
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 Wed Apr 02 09:53:23 GMT 2025
Edited
by admin
on Wed Apr 02 09:53:23 GMT 2025
Record UNII
EPL8W5565D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PROGLUMIDE
INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
NULSA
Preferred Name English
PROGLUMIDE [MI]
Common Name English
CR-242
Code English
ULCUTIN
Brand Name English
PROGLUMIDE [JAN]
Common Name English
Proglumide [WHO-DD]
Common Name English
MILID
Brand Name English
XYLAMIDE
Brand Name English
GASTROTOPIC
Brand Name English
BINOSIDE
Brand Name English
MIDELID
Brand Name English
(±)-4-BENZAMIDO-N,N-DIPROPYLGLUTARAMIC ACID
Systematic Name English
PROGLUMIDE [MART.]
Common Name English
proglumide [INN]
Common Name English
W-5219
Code English
PROMID
Brand Name English
4-(BENZOYLAMINO)-5-(DIPROPYLAMINO)-5-OXOPENTANOIC ACID
Systematic Name English
XYDE
Brand Name English
PENTANOIC ACID, 4-(BENZOYLAMINO)-5-(DIPROPYLAMINO)-5-OXO-, (±)-
Common Name English
DL-PROGLUMIDE
Common Name English
PROGLUMIDE [USAN]
Common Name English
NSC-757841
Code English
GLUTARAMIC ACID, 4-BENZAMIDO-N,N-DIPROPYL-, DL-
Common Name English
Classification Tree Code System Code
WHO-ATC A02BX06
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
NCI_THESAURUS C28197
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
FDA ORPHAN DRUG 762120
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
FDA ORPHAN DRUG 743020
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
FDA ORPHAN DRUG 756620
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
WHO-VATC QA02BX06
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
NCI_THESAURUS C29701
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
Code System Code Type Description
FDA UNII
EPL8W5565D
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
NSC
757841
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
CHEBI
32058
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
PUBCHEM
4922
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
NCI_THESAURUS
C81916
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
CAS
25727-74-6
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
SUPERSEDED
DRUG CENTRAL
2281
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
WIKIPEDIA
PROGLUMIDE
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
RXCUI
8730
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY RxNorm
EPA CompTox
DTXSID7023516
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
ChEMBL
CHEMBL316561
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
INN
2161
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
MERCK INDEX
m9161
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY Merck Index
ECHA (EC/EINECS)
229-567-4
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
MESH
D011377
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
DRUG BANK
DB13431
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
CAS
24485-90-3
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
SUPERSEDED
CAS
6620-60-6
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
EVMPD
SUB10078MIG
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
SMS_ID
100000081122
Created by admin on Wed Apr 02 09:53:23 GMT 2025 , Edited by admin on Wed Apr 02 09:53:23 GMT 2025
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> AGONIST
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY