PROGLUMIDE

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 Search

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
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
Cholecystokinin A receptor 7 Target ID: CHEMBL2871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2299627	Antagonist 2778		250.0 µM [IC50]
Cholecystokinin B receptor 9 Target ID: CHEMBL298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2299627	Antagonist 2778		900.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Peptic ulcer 72 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2741440	Primary		Approved 8429	Proglumide Approved Use Unknown

PubMed

Title	Date	PubMed
Effects of short term treatment with pentagastrin, proglumide, tamoxifen given separately or together with 5-fluorouracil on the growth in the murine transplantable Colon 38 cancer.	2001	11478694
Effect of three nonpeptide cholecystokinin antagonists on human isolated gallbladder.	2001 Dec	11768273
Synthesis, molecular modeling and QSAR studies in chiral 2,3-disubstituted-1,2,3,4-tetrahydro-9H-pyrido(3,4-b)indoles as potential modulators of opioid antinociception.	2001 Jun	11408175
Eradication of Helicobacter pylori restores the inhibitory effect of cholecystokinin on gastric motility in duodenal ulcer patients.	2001 Mar	11305509
Inhibition of the preferential binding of actin to the N-terminal hydratase domain of the 78-kDa gastrin-binding protein by non-steroidal anti-inflammatory drugs and gastrin receptor antagonists.	2001 May 1	11301046
CCK1 central receptor antagonist prevented the intestinal stress symptoms in sheep.	2002	11944584
Modulation of cholestasis-induced antinociception by CCK receptor agonists and antagonists.	2002 Apr	11872326
Inhibitory effect of loxiglumide (CR 1505), a cholecystokinin receptor antagonist, on N-nitrosobis(2-oxopropyl) amine-induced biliary carcinogenesis in Syrian hamsters.	2002 Mar	11865375
Cholecystokinin reduces ethanol consumption in golden hamsters.	2003 Apr	12798973
Enterostatin inhibition of dietary fat intake is dependent on CCK-A receptors.	2003 Aug	12855414
Effect of cholecystokinin1 receptor antagonist loxiglumide (CR1505) on basal pancreatic exocrine secretion in conscious rats.	2003 Jan	12499923
Effect of Dai-kenchu-to (Da-Jian-Zhong-Tang) on the delayed intestinal propulsion induced by chlorpromazine in mice.	2003 May	12686439
Sensitive SPE-HPLC method to determine a novel angiotensin-AT1 antagonist in biological samples.	2004 Apr 16	15063465
Effects of juice from Morinda citrifolia (Noni) on gastric emptying in male rats.	2004 Dec 31	15803749
Anxiogenic effect of cholecystokinin in the dorsal periaqueductal gray.	2004 Jan	14583742
Involvement of capsaicin-sensitive afferent nerves and cholecystokinin 2/gastrin receptors in gastroprotection and adaptation of gastric mucosa to Helicobacter pylori-lipopolysaccharide.	2004 Jul	15024038
Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin.	2004 Mar 17	15028763
Effect of lipopolysaccharide on expression and characterization of cholecystokinin receptors in rat pulmonary interstitial macrophages.	2004 Oct	15456538
Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids.	2005 Apr 6	15814788
Cholecystokinin octapeptide improves cardiac function by activating cholecystokinin octapeptide receptor in endotoxic shock rats.	2005 Jun 14	15948246
Role of cholecystokinin in appetite control and body weight regulation.	2005 Nov	16246215
The combined effects of proglumide and fluorouracil on the growth of murine Colon 38 cancer cells in vitro.	2005 Nov-Dec	16821214
Cholecystokinin octapeptide increases spontaneous glutamatergic synaptic transmission to neurons of the nucleus tractus solitarius centralis.	2005 Oct	16093341
Cholecystokinin1 receptors mediate the increase in Fos-like immunoreactivity in the rat myenteric plexus following intestinal oleate infusion.	2005 Sep 15	16098547
CCK1 antagonists: are they ready for clinical use?	2006	16699265
Anthranilic acid based CCK1 receptor antagonists and CCK-8 have a common step in their "receptor desmodynamic processes".	2006 Apr 20	16610788
Estrogen and CCK1 receptor modification of mu-opioid receptor binding in the cortex of female rats.	2006 Feb 16	16472782
Effects of the cholecystokinin A receptor antagonist loxiglumide on the proliferation and cell cycle time of pancreatic acinar cells in rats.	2006 Mar	16552340
Caerulein-induced acute pancreatitis in mice that constitutively overexpress Reg/PAP genes.	2006 May 15	16700916
Estrogen receptor alpha-induced cholecystokinin type A receptor expression in the female mouse pituitary.	2007 Dec	18000302
Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake.	2007 Oct	17634201

Patents

Sample Use Guides

In Vivo Use Guide

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 `Sat Dec 16 17:59:01 GMT 2023` Edited by `admin` on `Sat Dec 16 17:59:01 GMT 2023`
Record UNII	EPL8W5565D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PROGLUMIDE

Official 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

NULSA

Brand 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