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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

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
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
Pharmacology of cardiovascular chronotherapeutic agents.
2001 Sep
Effects of grapefruit juice and smoking on verapamil concentrations in steady state.
2002 Apr
Chrono: a community-based hypertension trial of a chronotherapeutic formulation of verapamil.
2002 Nov-Dec
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
[Possibilities for prolonging the maximal time for kidney ischemia in using different variants of anti-ischemic protection].
2003 May-Jun
(R)- and (S)-[11C]verapamil as PET-tracers for measuring P-glycoprotein function: in vitro and in vivo evaluation.
2003 Oct
Novel chewable sustained-release tablet containing verapamil hydrochloride.
2004
Pharmacodynamics of controlled release verapamil in patients with hypertension: an analysis using spline functions.
2004 Jul
[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
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
Cell death-mediated antiviral effect of chitosan in tobacco.
2006 Nov-Dec
Corn oil supplementation to steers grazing endophyte-free tall fescue. I. Effects on in vivo digestibility, performance, and carcass traits.
2007 May
[A 48-year-old woman's survival from a massive verapamil overdose].
2007 Nov 19
Effects of restricted feeding of beef heifers during the postweaning period on growth, efficiency, and ultrasound carcass characteristics.
2007 Oct
(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
Strategies for enhanced drug delivery to the central nervous system.
2008 Mar-Apr
Effects of divergent selection for serum insulin-like growth factor-I concentration on performance, feed efficiency, and ultrasound measures of carcass composition traits in Angus bulls and heifers.
2008 Nov
Exploring enantiospecific ligand-protein interactions using cellular membrane affinity chromatography: chiral recognition as a dynamic process.
2008 Nov 1
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
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
The effect of infliximab on hepatic cytochrome P450 and pharmacokinetics of verapamil in rats with pre-adjuvant arthritis: a drug-disease and drug-drug interaction.
2009 Jul
Different effects of ketoconazole on the stereoselective first-pass metabolism of R/S-verapamil in the intestine and the liver: important for the mechanistic understanding of first-pass drug-drug interactions.
2009 Nov
Focus on adoptive T cell transfer trials in melanoma.
2010
Impact of reduced marker set estimation of genomic relationship matrices on genomic selection for feed efficiency in Angus cattle.
2010 Apr 19
(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
Development of 2D chiral chromatography with accelerator mass spectrometry for quantification of (14)C-labeled R- and S-verapamil in plasma.
2010 Mar
Pigeon peas as a supplement for lactating dairy cows fed corn silage-based diets.
2010 Nov
Effect of feeding alfalfa hay or Tifton 85 bermudagrass haylage with or without a cellulase enzyme on performance of Holstein cows.
2010 Nov
Assessment of pulmonary function and serum substance levels in newborn and juvenile rats.
2010 Nov
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.
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 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID501009404
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
EVMPD
SUB07056MIG
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
FDA UNII
QR5PYD126V
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
ECHA (EC/EINECS)
253-878-4
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
CHEBI
77734
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
ChEMBL
CHEMBL197
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
SMS_ID
100000082900
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
NCI_THESAURUS
C1563
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
MERCK INDEX
m11414
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY Merck Index
PUBCHEM
65808
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
DRUG BANK
DB14063
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
INN
6813
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
CAS
38321-02-7
Created by admin on Sat Dec 16 16:22:50 UTC 2023 , Edited by admin on Sat Dec 16 16:22:50 UTC 2023
PRIMARY
ACTIVE MOIETY
Structure of DEXVERAPAMIL
SALT/SOLVATE (PARENT)
Structure of DEXVERAPAMIL HYDROCHLORIDE
NIH
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