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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.

Originator

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

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P08183
Gene ID: 5243.0
Gene Symbol: ABCB1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
REZULAR

Approved Use

Unknown
Preventing
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2103 ng/mL
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
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
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
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
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
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
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
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
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
Reversal of multidrug resistance and increase in plasma membrane fluidity in CHO cells with R-verapamil and bile salts.
2001 Mar
Disposition and pharmacologic effects of R/S-verapamil in patients with chronic atrial fibrillation: an investigation comparing single and multiple dosing.
2001 May
Pharmacokinetics of controlled-release verapamil in healthy volunteers and patients with hypertension or angina.
2002 Jan
Differential effects of the optical isomers of KR30031 on cardiotoxicity and on multidrug resistance reversal activity.
2003 Feb
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
[Possibilities for prolonging the maximal time for kidney ischemia in using different variants of anti-ischemic protection].
2003 May-Jun
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
Effect of early phase adjuvant arthritis on hepatic P450 enzymes and pharmacokinetics of verapamil: an alternative approach to the use of an animal model of inflammation for pharmacokinetic studies.
2005 Apr
Development and characterization of an immobilized human organic cation transporter based liquid chromatographic stationary phase.
2005 Apr 25
Littoral cell angioma of the spleen treated by laparoscopic splenectomy.
2005 Apr-Jun
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
Effects of rhubarb on isolated gastric muscle strips of guinea pigs.
2005 May 7
Multidrug resistance: retrospect and prospects in anti-cancer drug treatment.
2006
Cell death-mediated antiviral effect of chitosan in tobacco.
2006 Nov-Dec
The effect of gender on the pharmacokinetics of verapamil and norverapamil in human.
2006 Oct
Cytochrome P450 3A5 genotype is associated with verapamil response in healthy subjects.
2007 Nov
[A 48-year-old woman's survival from a massive verapamil overdose].
2007 Nov 19
(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
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
Corn oil or corn grain supplementation to steers grazing endophyte-free tall fescue. I. Effects on in vivo digestibility, performance, and carcass quality.
2008 Nov
High-Resolution Images with Minimum Energy Dissipation and Maximum Field-of-View in Camera-Based Wireless Multimedia Sensor Networks.
2009
Pretreatment with R(+)-verapamil significantly reduces mortality and cytokine expression in murine model of septic shock.
2009 Apr
Effect of calcium-regulating hormones and calcium channel modulators on glucose consumption by muscle and adipose tissues in vivo and in vitro.
2009 Aug
Determinants of quality of life of youths in an English-speaking Caribbean nation.
2009 Dec
Phenotypic and genetic relationships of residual feed intake with performance and ultrasound carcass traits in Brangus heifers.
2009 Dec
(E)-4-Bromo-N-(2,3-dimeth-oxy-benzyl-idene)aniline.
2010 Aug 4
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
Development of 2D chiral chromatography with accelerator mass spectrometry for quantification of (14)C-labeled R- and S-verapamil in plasma.
2010 Mar
Hypertension, antihypertensive medication use, and breast cancer risk in the California Teachers Study cohort.
2010 Oct
Patents

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
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SALT/SOLVATE -> PARENT
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ACTIVE MOIETY