LOXIGLUMIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H30Cl2N2O5
Molecular Weight	461.379
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCN(CCCOC)C(=O)C(CCC(O)=O)NC(=O)C1=CC(Cl)=C(Cl)C=C1

InChI

InChIKey=QNQZBKQEIFTHFZ-UHFFFAOYSA-N

InChI=1S/C21H30Cl2N2O5/c1-3-4-5-11-25(12-6-13-30-2)21(29)18(9-10-19(26)27)24-20(28)15-7-8-16(22)17(23)14-15/h7-8,14,18H,3-6,9-13H2,1-2H3,(H,24,28)(H,26,27)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9522034 | https://www.ncbi.nlm.nih.gov/pubmed/11247838 | https://www.ncbi.nlm.nih.gov/pubmed/9368707

Loxiglumide is a potent, orally active, and selective CCK-A receptor antagonist which stimulates calorie intake and hunger feelings in humans. Loxiglumide inhibits pancreatic secretion of digestive enzymes, and also blocks CCK-induced gastric secretions and emptying. Intravenous administration of loxiglumide antagonized the CCK-induced reduction of gastric emptying in rats, acceleration of intestinal transport in mice, increase in ileal motility in rabbits, gallbladder contraction in guinea pigs and acceleration of gallbladder emptying in mice.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cholecystokinin A receptor 7 Target ID: CHEMBL1901 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16610788 \| https://www.ncbi.nlm.nih.gov/pubmed/3663268	Antagonist 2778		195.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pancreatitis 16 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16552340 https://www.ncbi.nlm.nih.gov/pubmed/12131781 https://www.ncbi.nlm.nih.gov/pubmed/10026438	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
12.7 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2619779	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:		LOXIGLUMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.9 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2619779	400 mg 2 times / day single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		LOXIGLUMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
109.8 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2619779	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:		LOXIGLUMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
60.6 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2619779	400 mg 2 times / day single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		LOXIGLUMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
800 mg 3 times / day multiple, oral Highest studied dose Dose: 800 mg, 3 times / day Route: oral Route: multiple Dose: 800 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9094151 Page: p.225	unhealthy, ADULT n = 32 Health Status: unhealthy Condition: pancreatic cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/9094151 Page: p.225	Sources: https://pubmed.ncbi.nlm.nih.gov/9094151 Page: p.225
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: https://pubmed.ncbi.nlm.nih.gov/12131781 Page: e3	unhealthy, ADULT n = 50 Health Status: unhealthy Condition: pancreatitis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/12131781 Page: e3	Sources: https://pubmed.ncbi.nlm.nih.gov/12131781 Page: e3
50 mg single, intravenous Studied dose Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12895218 Page: p.335	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: biliary tract disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/12895218 Page: p.335	Sources: https://pubmed.ncbi.nlm.nih.gov/12895218 Page: p.335

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	rCYP 1

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170465971	inconclusive [IC50 19.4971 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170465971	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170465971	yes [IC50 19.4971 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
rCYP 1	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9406280/	no

PubMed

Title	Date	PubMed
Pharmacological characterisation of a new potent and specific nonpolypeptidic cholecystokinin antagonist.	1987 Jun	3663268

Patents

Sample Use Guides

In Vivo Use Guide

chronic pancreatitis: oral treatment with loxiglumide (300, 600, and 1,200 mg/d) for 4 weeks.

Route of Administration: Oral

In Vitro Use Guide

Loxiglumide inhibited 125I-CCK-8 binding to rat pancreatic and bovine gallbladder membranes with IC50 values of 195 and 77.1 nmol/l, respectively. Loxiglumide also inhibited 125I-CCK-8 binding to guinea pig cerebral cortex membranes and parietal cells with IC50 values of 12363 and 15455 nmol/l, respectively. In addition, loxiglumide inhibited 125I-gastrin binding to guinea pig parietal cells with IC50 values of 6134 nmol/l.

Name

Type

Language

LOXIGLUMIDE

Official Name

English

loxiglumide [INN]

Common Name

English

LOXIGLUMIDE [JAN]

Common Name

English

(±)-4-(3,4-DICHLOROBENZAMIDO)-N-(3-METHOXYPROPYL)-N-PENTYLGLUTARAMIC ACID

Systematic Name

English

LOXIGLUMIDE [MART.]

Common Name

English

CR-1505

Code

English

LOXIGLUMIDE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C28197