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
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
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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/17646169 | http://www.google.ch/patents/US5889060http://adisinsight.springer.com/drugs/800007413Curator'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/
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17646169 | http://www.google.ch/patents/US5889060http://adisinsight.springer.com/drugs/800007413
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
Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1767178 | http://adisinsight.springer.com/drugs/800007413
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P08183 Gene ID: 5243.0 Gene Symbol: ABCB1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17646169 |
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Target ID: CHEMBL3004 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17646169 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | REZULAR Approved UseUnknown |
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Preventing | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Sources: http://www.google.ch/patents/US5889060 |
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Title | Date | PubMed |
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Reversal of multidrug resistance and increase in plasma membrane fluidity in CHO cells with R-verapamil and bile salts. | 2001 Mar |
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Disposition and pharmacologic effects of R/S-verapamil in patients with chronic atrial fibrillation: an investigation comparing single and multiple dosing. | 2001 May |
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Pharmacokinetics of controlled-release verapamil in healthy volunteers and patients with hypertension or angina. | 2002 Jan |
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Differential effects of the optical isomers of KR30031 on cardiotoxicity and on multidrug resistance reversal activity. | 2003 Feb |
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Optimizing the level of wet corn gluten feed in the diet of lactating dairy cows. | 2003 Mar |
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Enantioselective transport and CYP3A4-mediated metabolism of R/S-verapamil in Caco-2 cell monolayers. | 2003 May |
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[Possibilities for prolonging the maximal time for kidney ischemia in using different variants of anti-ischemic protection]. | 2003 May-Jun |
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Novel chewable sustained-release tablet containing verapamil hydrochloride. | 2004 |
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Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. | 2004 Feb |
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N-hexanoyl-sphingomyelin potentiates in vitro doxorubicin cytotoxicity by enhancing its cellular influx. | 2004 Feb 23 |
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Actions of R- and S-verapamil and nifedipine on rat vascular and intestinal smooth muscle. | 2004 Jul |
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Pharmacodynamics of controlled release verapamil in patients with hypertension: an analysis using spline functions. | 2004 Jul |
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Effect of supranutritional and organically bound selenium on performance, carcass characteristics, and selenium distribution in finishing beef steers. | 2004 May |
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Nonstructural carbohydrate supplementation of yearling heifers and range beef cows. | 2004 Sep |
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[Endothelium of myocardium microvessel under conditions of hypothermia, ischemia, reperfusion and pharmaco-cold cardioplegia with calcium antagonist]. | 2005 |
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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 |
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Development and characterization of an immobilized human organic cation transporter based liquid chromatographic stationary phase. | 2005 Apr 25 |
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Littoral cell angioma of the spleen treated by laparoscopic splenectomy. | 2005 Apr-Jun |
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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 |
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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 |
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Effects of rhubarb on isolated gastric muscle strips of guinea pigs. | 2005 May 7 |
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Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. | 2006 |
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Cell death-mediated antiviral effect of chitosan in tobacco. | 2006 Nov-Dec |
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The effect of gender on the pharmacokinetics of verapamil and norverapamil in human. | 2006 Oct |
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Cytochrome P450 3A5 genotype is associated with verapamil response in healthy subjects. | 2007 Nov |
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[A 48-year-old woman's survival from a massive verapamil overdose]. | 2007 Nov 19 |
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(R)- and (S)-verapamil differentially modulate the multidrug-resistant protein MRP1. | 2007 Oct 26 |
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Manure nutrient excretion by lactating cows fed exogenous phytase and cellulase. | 2007 Sep |
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Studies of verapamil binding to human serum albumin by high-performance affinity chromatography. | 2008 Dec 1 |
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Efficacy of AZM therapy in patients with gingival overgrowth induced by Cyclosporine A: a systematic review. | 2008 Dec 16 |
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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 |
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High-Resolution Images with Minimum Energy Dissipation and Maximum Field-of-View in Camera-Based Wireless Multimedia Sensor Networks. | 2009 |
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Pretreatment with R(+)-verapamil significantly reduces mortality and cytokine expression in murine model of septic shock. | 2009 Apr |
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Effect of calcium-regulating hormones and calcium channel modulators on glucose consumption by muscle and adipose tissues in vivo and in vitro. | 2009 Aug |
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Determinants of quality of life of youths in an English-speaking Caribbean nation. | 2009 Dec |
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Phenotypic and genetic relationships of residual feed intake with performance and ultrasound carcass traits in Brangus heifers. | 2009 Dec |
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(E)-4-Bromo-N-(2,3-dimeth-oxy-benzyl-idene)aniline. | 2010 Aug 4 |
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Unresolved abdominal mass in an adult cryptorchid testis: a case report. | 2010 Dec 7 |
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(E)-4-Bromo-N-(2,3,4-trimeth-oxy-benzyl-idene)aniline. | 2010 Jul 21 |
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Development of 2D chiral chromatography with accelerator mass spectrometry for quantification of (14)C-labeled R- and S-verapamil in plasma. | 2010 Mar |
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Hypertension, antihypertensive medication use, and breast cancer risk in the California Teachers Study cohort. | 2010 Oct |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: http://www.google.ch/patents/US5889060
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17646169
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
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admin
on
Edited
Sat Dec 16 16:22:50 GMT 2023
by
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on
Sat Dec 16 16:22:50 GMT 2023
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Record UNII |
QR5PYD126V
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C333
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SUB07056MIG
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR |
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SALT/SOLVATE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |