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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H38N2O4
Molecular Weight 454.6016
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DEXVERAPAMIL

SMILES

COC1=C(OC)C=C(CCN(C)CCC[C@@](C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1

InChI

InChIKey=SGTNSNPWRIOYBX-HHHXNRCGSA-N
InChI=1S/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3/t27-/m1/s1

HIDE SMILES / InChI
Molecular Formula C27H38N2O4
Molecular Weight 454.6016
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17646169 | http://adisinsight.springer.com/drugs/800022706 | http://www.drugdevelopment-technology.com/projects/rezular/

Dexverapamil (R-verapamil) is an enantiomer of verapamil. R-isomer behaved as an inhibitor of multidrug-resistant protein MRP1 (involved in the cancer cell multidrug resistance phenotype). It was developed by Knoll (BASF Pharma) as a chemosensitiser and/or modulator of multidrug resistance for use in combination with cancer chemotherapy. Dexverapamil was undergoing phase II clinical studies in France, Italy, Spain, United Kingdom and the US in patients with various cancers. It was also undergoing phase I clinical trials in Japan where it was licensed to Mitsui and Mitsui Toatsu Chemicals. However, development was discontinued. Dexverapamil (R-verapamil) has been developing by AGI therapeutics for the treatment of Irritable bowel syndrome however development was discontinued.

CNS Activity

Originator

Knoll
18
Curator's Comment: Verapamil was fisrt synthetized by German pharmaceutical firm Knoll (D365). Verapamil is a recamic mixture of R and S enantiomers. R-verapamil has been developing by AGI therapeutics for the treatment of Irritable bowel syndrome. http://adisinsight.springer.com/drugs/800022706

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Multidrug resistance protein 1
8
Target ID: P08183
Gene ID: 5243.0
Gene Symbol: ABCB1
Target Organism: Homo sapiens (Human)
Inhibitor
8297
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
REZULAR

Approved Use

Unknown
Preventing
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Not Provided
504
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2103 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
308 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
892 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
11818 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1707 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3974 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5.6 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8398588/
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEXVERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
[Isoptin in the therapy of supraventricular arrhythmia in patients with diabetes mellitus, non-insulin dependent, concurrent with ischemic heart disease].
2001 Sep-Dec
[Verapamil retard as a medication for the prevention of affective and schizoaffective psychosis relapses].
2002
[Efficiency of antiarrhythmic drugs of class 1C and isoptin in paroxysmal supraventricular tachycardia].
2002
Pharmacokinetics of controlled-release verapamil in healthy volunteers and patients with hypertension or angina.
2002 Jan
Chrono: a community-based hypertension trial of a chronotherapeutic formulation of verapamil.
2002 Nov-Dec
Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer: implications for drug therapy.
2002 Sep 9
Population analyses of sustained-release verapamil in patients: effects of sex, race, and smoking.
2003 Jan
Optimizing the level of wet corn gluten feed in the diet of lactating dairy cows.
2003 Mar
Enantioselective transport and CYP3A4-mediated metabolism of R/S-verapamil in Caco-2 cell monolayers.
2003 May
Novel chewable sustained-release tablet containing verapamil hydrochloride.
2004
Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites.
2004 Feb
N-hexanoyl-sphingomyelin potentiates in vitro doxorubicin cytotoxicity by enhancing its cellular influx.
2004 Feb 23
Actions of R- and S-verapamil and nifedipine on rat vascular and intestinal smooth muscle.
2004 Jul
Pharmacodynamics of controlled release verapamil in patients with hypertension: an analysis using spline functions.
2004 Jul
Effect of supranutritional and organically bound selenium on performance, carcass characteristics, and selenium distribution in finishing beef steers.
2004 May
Nonstructural carbohydrate supplementation of yearling heifers and range beef cows.
2004 Sep
[Endothelium of myocardium microvessel under conditions of hypothermia, ischemia, reperfusion and pharmaco-cold cardioplegia with calcium antagonist].
2005
[Efficacy of and tolerance to combined therapy with dihydropyridine and non-dihydropyridine Ca antagonists in patients with moderate arterial hypertension].
2005
Development and characterization of an immobilized human organic cation transporter based liquid chromatographic stationary phase.
2005 Apr 25
Phosphorus-doped and undoped glassy carbon indicator electrodes in controlled-current potentiometric titrations of bromide- or chloride-containing active ingredients in some pharmaceutical preparations.
2005 Feb 23
Efficacy of using a combination of rendered protein products as an undegradable intake protein supplement for lactating, winter-calving, beef cows fed bromegrass hay.
2005 Jan
Multidrug resistance: retrospect and prospects in anti-cancer drug treatment.
2006
Cardiovascular effects of (R)- and (S)-verapamil and racemic verapamil in humans: a placebo-controlled study.
2006 Aug
The effect of short- and long-term administration of verapamil on the disposition of cytochrome P450 3A and P-glycoprotein substrates.
2006 Mar
Corn oil supplementation to steers grazing endophyte-free tall fescue. I. Effects on in vivo digestibility, performance, and carcass traits.
2007 May
Cytochrome P450 3A5 genotype is associated with verapamil response in healthy subjects.
2007 Nov
(R)- and (S)-verapamil differentially modulate the multidrug-resistant protein MRP1.
2007 Oct 26
Manure nutrient excretion by lactating cows fed exogenous phytase and cellulase.
2007 Sep
Pancreatic mass, cellularity, and alpha-amylase and trypsin activity in feedlot steers fed diets differing in crude protein concentration.
2008 Apr
Studies of verapamil binding to human serum albumin by high-performance affinity chromatography.
2008 Dec 1
Efficacy of AZM therapy in patients with gingival overgrowth induced by Cyclosporine A: a systematic review.
2008 Dec 16
Strategies for enhanced drug delivery to the central nervous system.
2008 Mar-Apr
High-Resolution Images with Minimum Energy Dissipation and Maximum Field-of-View in Camera-Based Wireless Multimedia Sensor Networks.
2009
Role of multidrug transporters in neurotherapeutics.
2009 Apr
Focus on adoptive T cell transfer trials in melanoma.
2010
(E)-4-Bromo-N-(2,3-dimeth-oxy-benzyl-idene)aniline.
2010 Aug 4
Metabolic activity and mRNA levels of human cardiac CYP450s involved in drug metabolism.
2010 Dec 14
Unresolved abdominal mass in an adult cryptorchid testis: a case report.
2010 Dec 7
(E)-4-Bromo-N-(2,3,4-trimeth-oxy-benzyl-idene)aniline.
2010 Jul 21
The synthesis and characterization of cellular membrane affinity chromatography columns for the study of human multidrug resistant proteins MRP1, MRP2 and human breast cancer resistant protein BCRP using membranes obtained from Spodoptera frugiperda (Sf9) insect cells.
2010 Jun 15
Hypertension, antihypertensive medication use, and breast cancer risk in the California Teachers Study cohort.
2010 Oct
Patents

Patents

JP2011525180A
180
US5889060
2

Sample Use Guides

In Vivo Use Guide
Administration of (R)-verapamil may be by any of the conventional routes, for instance oral, intravenous, sublingual, topical and rectal. Conventional formulations may verapamil will be formulated for oral administration. Typically, a suitable dosage of the active component is up to 500 mg per day, but any of the standard dosages for the racemate may be used.
Route of Administration: Other
In Vitro Use Guide
Curator's Comment: in vitro dexverapamil can enhance doxorubicin cytotoxicity in P388/Dx cells with a much greater effect depending on the treatment scheme used, by increasing the intracellular content of drug. https://www.ncbi.nlm.nih.gov/pubmed/9199659/
It was investigated the individual effects of each enantiomer by comparison with the racemic mixture. The cellular effects were tested on both control and human MRP1 cDNA-transfected baby hamster kidney 21 (BHK-21) cells (MRP1-BHK-21). Racemic verapamil was cytotoxic for MRP1-BHK-21 cells at concentrations <10-20 μM, which were ineffective in control BHK-21 cells. The R- and S-enantiomers were highly discriminated because (R)-verapamil did not exhibit any cytotoxicity for the two types of cell, whereas (S)-verapamil displayed a killing activity, even more potent than that observed with the racemic mixture at the same concentration.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:22:50 GMT 2023
Edited
by admin
on Sat Dec 16 16:22:50 GMT 2023
Record UNII
QR5PYD126V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DEXVERAPAMIL
INN  
INN  
Official Name English
(R)-(+)-VERAPAMIL
Common Name English
(R)-VERAPAMIL
Common Name English
VERAPAMIL (R)-FORM [MI]
Common Name English
VERAPAMIL, (R)-
Common Name English
(+)-(R)-VERAPAMIL
Common Name English
VERAPAMIL, (+)-(R)-
Common Name English
(+)-VERAPAMIL
Common Name English
VERAPAMIL, (R)-(+)-
Common Name English
dexverapamil [INN]
Common Name English
BENZENEACETONITRILE, .ALPHA.-(3-((2-(3,4-DIMETHOXYPHENYL)ETHYL)METHYLAMINO)PROPYL)-3,4-DIMETHOXY-.ALPHA.-(1-METHYLETHYL)-, (R)-
Systematic Name English
(.ALPHA.R)-.ALPHA.-(3-((2-(3,4-DIMETHOXYPHENYL)ETHYL)METHYLAMINO)PROPYL)-3,4-DIMETHOXY-.ALPHA.-(1-METHYLETHYL)BENZENEACETONITRILE
Systematic Name English
(+)-(R)-5-((3,4-DIMETHOXYPHENETHYL)METHYLAMINO)-2-(3,4-DIMETHOXYPHENYL)-2-ISOPROPYLVALERONITRILE
Systematic Name English
VERAPAMIL, (+)-
Common Name English
D-VERAPAMIL
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C333
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID501009404
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
EVMPD
SUB07056MIG
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
FDA UNII
QR5PYD126V
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
ECHA (EC/EINECS)
253-878-4
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
CHEBI
77734
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
ChEMBL
CHEMBL197
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
SMS_ID
100000082900
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
NCI_THESAURUS
C1563
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
MERCK INDEX
m11414
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY Merck Index
PUBCHEM
65808
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
DRUG BANK
DB14063
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
INN
6813
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
CAS
38321-02-7
Created by admin on Sat Dec 16 16:22:50 GMT 2023 , Edited by admin on Sat Dec 16 16:22:50 GMT 2023
PRIMARY
Related Record Type Details
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
Structure of DEXVERAPAMIL HYDROCHLORIDE
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of DEXVERAPAMIL
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