DEXTOFISOPAM

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H26N2O4
Molecular Weight	382.4528
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC[C@@H]1C2=C(C=C(OC)C(OC)=C2)C(=NN=C1C)C3=CC(OC)=C(OC)C=C3

InChI

InChIKey=RUJBDQSFYCKFAA-HNNXBMFYSA-N

InChI=1S/C22H26N2O4/c1-7-15-13(2)23-24-22(14-8-9-18(25-3)19(10-14)26-4)17-12-21(28-6)20(27-5)11-16(15)17/h8-12,15H,7H2,1-6H3/t15-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C22H26N2O4
Molecular Weight	382.4528
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.wikinvest.com/stock/Pharmos_(PARS)/Filing/10-K/2008/F5438184 | http://www.medscape.com/viewarticle/568560 | https://www.ncbi.nlm.nih.gov/pubmed/17973974

Dextofisopam, a non-serotonergic agent currently being evaluated for the treatment of irritable bowel syndrome (IBS), is the R-enantiomer of racemic tofisopam, a molecule marketed and used safely outside the United States for over three decades for multiple indications including IBS. Dextofisopam represents a novel, first-in-class opportunity with a positive proof-of-concept study in an arena where there are few compounds with unique approaches or positive efficacy results. By structure, Dextofisopam is a member of the homophthalazine class; Dextofisopam binds to specific receptors in areas of the brain affecting autonomic function, including gastrointestinal (GI) function. Unlike the two 5-HT3 or 5-HT4 mediated IBS therapies currently available, both with significant safety concerns, Dextofisopam novel non-serotonergic activity offers a unique and innovative approach to IBS treatment. Recent studies have indicated that dextofisopam binds to a novel binding site within the central nervous system that may be responsible for mediating its actions. This receptor has been characterized as the 2,3-benzodiazepine receptor, which is distinct from the classical 1,4 or 1,5-benzodiazepine receptor. Dextofisopam has no significant binding at other receptors or ion channels

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; benzodiazepine site 38 Target ID: CHEMBL2109243 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D03737 \| http://www.crystalsoftwaredesign.com/VelaPharm/images/ACG.pdf	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Irritable bowel syndrome 61 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17973974 http://adisinsight.springer.com/drugs/800017944	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
756 ng/mL OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
402 ng/mL OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1508 ng/mL OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1251 ng/mL OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1729 ng × h/mL OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
844 ng × h/mL OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3338 ng × h/mL OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3490 ng × h/mL OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
10.15 h OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.2 h OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.1 h OTHER https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DEXTOFISOPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease	Sources: https://www.researchgate.net/publication/228774168_The_potential_of_dextofisopam_for_treatment_of_irritable_bowel_syndrome_and_inflammatory_bowel_disease
200 mg 2 times / day multiple, oral Studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17973974	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17973974	Disc. AE: Pancreatitis... AEs leading to discontinuation/dose reduction: Pancreatitis (1.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/17973974

AEs

AE	Significance	Dose	Population
Pancreatitis	1.5% Disc. AE	200 mg 2 times / day multiple, oral Studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17973974	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17973974

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A5 446 CYP2C19 1119

Drug as victim

Target	Modality	Activity
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17646282/	likely
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17646282/	major [Km 20 uM]
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17646282/	major [Km 7.6 uM]
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17646282/	yes [Km 0.9 uM]
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17646282/	yes [Km 17 uM]

PubMed

Title	Date	PubMed
Clinical trial: dextofisopam in the treatment of patients with diarrhoea-predominant or alternating irritable bowel syndrome.	2008-01-15	17973974
Gateways to clinical trials.	2006-10	17136234
Personal view: adequate relief as a primary endpoint in irritable bowel syndrome.	2006-04-01	16573790
Gateways to clinical trials.	2005-04	15834452

Patents

Sample Use Guides

In Vivo Use Guide

100, 200, and 300 mg BID for 12 weeks

Route of Administration: Oral

In Vitro Use Guide

Incubations containing 500 ng/ml (1.3 uM) (R)-tofisopam (Dextofisopam) were carried out with 0.05, 0.2, and 1.0 mg/ml pooled human liver microsomes.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 06:59:37 GMT 2025` Edited by `admin` on `Wed Apr 02 06:59:37 GMT 2025`
Record UNII	EZ15I5D6C1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DEXTOFISOPAM

Official Name

English

R-TOFISOPAM

Preferred Name

English

dextofisopam [INN]

Common Name

English

DEXTOFISOPAM [USAN]

Common Name

English

5H-2,3-BENZODIAZEPINE, 1-(3,4-DIMETHOXYPHENYL)-5-ETHYL-7,8-DIMETHOXY-4-METHYL, (5R)

Common Name

English

(+)-(5R)-1-(3,4-DIMETHOXYPHENYL)-5-ETHYL-7,8-DIMETHOXY-4-METHYL-5H-2,3-BENZODIAZEPINE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29698