U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C27H38N2O4
Molecular Weight 454.6026
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VERAPAMIL

SMILES

CC(C)C(CCCN(C)CCc1ccc(c(c1)OC)OC)(C#N)c2ccc(c(c2)OC)OC

InChI

InChIKey=SGTNSNPWRIOYBX-UHFFFAOYSA-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

HIDE SMILES / InChI

Molecular Formula C27H38N2O4
Molecular Weight 454.6026
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00661

Verapamil is a FDA approved drug used to treat high blood pressure and to control chest pain. Verapamil is an L-type calcium channel blocker that also has antiarrythmic activity. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias. Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known.

CNS Activity

Curator's Comment:: it out of the brain.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CALAN

Approved Use

CALAN tablets are indicated for the treatment of the following: Angina 1. Angina at rest including: — Vasospastic (Prinzmetal’s variant) angina — Unstable (crescendo, pre-infarction) angina 2. Chronic stable angina (classic effort-associated angina) Arrhythmias 1. In association with digitalis for the control of ventricular rate at rest and during stress in patients with chronic atrial flutter and/or atrial fibrillation (see WARNINGS: Accessory bypass tract) 2. Prophylaxis of repetitive paroxysmal supraventricular tachycardia Essential hypertension CALAN is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug.

Launch Date

366336000000
Primary
CALAN

Approved Use

CALAN tablets are indicated for the treatment of the following: Angina 1. Angina at rest including: — Vasospastic (Prinzmetal’s variant) angina — Unstable (crescendo, pre-infarction) angina 2. Chronic stable angina (classic effort-associated angina) Arrhythmias 1. In association with digitalis for the control of ventricular rate at rest and during stress in patients with chronic atrial flutter and/or atrial fibrillation (see WARNINGS: Accessory bypass tract) 2. Prophylaxis of repetitive paroxysmal supraventricular tachycardia Essential hypertension CALAN is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug.

Launch Date

366336000000
Primary
CALAN

Approved Use

CALAN tablets are indicated for the treatment of the following: Angina 1. Angina at rest including: — Vasospastic (Prinzmetal’s variant) angina — Unstable (crescendo, pre-infarction) angina 2. Chronic stable angina (classic effort-associated angina) Arrhythmias 1. In association with digitalis for the control of ventricular rate at rest and during stress in patients with chronic atrial flutter and/or atrial fibrillation (see WARNINGS: Accessory bypass tract) 2. Prophylaxis of repetitive paroxysmal supraventricular tachycardia Essential hypertension CALAN is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug.

Launch Date

366336000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
139.28 ng/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
367.05 ng × h/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.15 h
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
9.9%
VERAPAMIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: Co-administration of multiple doses of 10 mg of verapamil with 80 mg simvastatin resulted in exposure to simvastatin 2.5-fold that following simvastatin alone; Clinically significant interactions have been reported with inhibitors of CYP3A4 (e.g., erythromycin, ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (e.g., rifampin) have caused a lowering of plasma levels of verapamil
Page: 7
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers.
2000 Feb
Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment.
2001 Feb
[Treatment of cluster headache].
2001 Feb
Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats.
2001 Feb
Refractory no-reflow successfully treated with local infusion of high-dose adenosine and verapamil--a case report.
2001 Feb
Selective drug resistant human osteosarcoma cell lines.
2001 Feb
Model organisms: new insights into ion channel and transporter function. L-type calcium channels regulate epithelial fluid transport in Drosophila melanogaster.
2001 Feb
A bioreversible prodrug approach designed to shift mechanism of brain uptake for amino-acid-containing anticancer agents.
2001 Feb
Pharmacologic management of atrial fibrillation: current therapeutic strategies.
2001 Feb
Dysfunction of polymorphonuclear leukocytes in uremia: role of parathyroid hormone.
2001 Feb
Intra- and intercellular Ca(2+)-transient propagation in normal and high glucose solutions in ROS cells during mechanical stimulation.
2001 Feb
L-type calcium channel blockers and EGTA enhance superoxide production in cardiac fibroblasts.
2001 Feb
Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia.
2001 Feb
Signaling mechanisms for the selective vasoconstrictor effect of norbormide on the rat small arteries.
2001 Feb
Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells.
2001 Feb
Pre- or post-ischemic treatment with a novel Na+/Ca2+ exchange inhibitor, KB-R7943, shows renal protective effects in rats with ischemic acute renal failure.
2001 Feb
Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone.
2001 Feb
A flow cell assay for evaluation of whole cell drug efflux kinetics: analysis of paclitaxel efflux in CCRF-CEM leukemia cells overexpressing P-glycoprotein.
2001 Feb
Ivermectin excretion by isolated functionally intact brain endothelial capillaries.
2001 Feb
Investigating the platelet-sparing mechanism of paclitaxel/carboplatin combination chemotherapy.
2001 Feb 1
Multidrug resistance protein (MRP) activity in normal mature leukocytes and CD34-positive hematopoietic cells from peripheral blood.
2001 Feb 2
Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery.
2001 Feb 2
Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats.
2001 Feb 2
hKv4.3 channel characterization and regulation by calcium channel antagonists.
2001 Feb 23
The stimulation of MAP kinase by 1,25(OH)(2)-vitamin D(3) in skeletal muscle cells is mediated by protein kinase C and calcium.
2001 Feb 28
Cardiovascular action of a cardioselective Ca(2+)channel blocker AH-1058 in conscious dogs assessed by telemetry.
2001 Feb 9
Involvement of cyclic GMP in nitric-oxide-induced gastric relaxation Comparison of the actions of cyclic GMP and cyclic AMP.
2001 Jan
Volume-weighted mean nuclear volume and numerical nuclear density in the cardiomyocyte following enalapril and verapamil treatment.
2001 Jan
Identification of an organic anion transport system in the human colon carcinoma cell line HT29 clone 19A.
2001 Jan
The effects of vasopressin in isolated rat hearts.
2001 Jan
Penetration of verapamil hydrochloride in the presence of sodium glycocholate as penetration enhancer through mucous membrane.
2001 Jan
Transport of [3H]MPP+ in an immortalized rat brain microvessel endothelial cell line (RBE 4).
2001 Jan
Ionized magnesium in the homeostasis of cells: intracellular threshold for Mg(2+) in human platelets.
2001 Jan
Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex.
2001 Jan
Sarcoglycan, the heart, and skeletal muscles: new treatment, old drug?
2001 Jan
Modulator activity of PSC 833 and cyclosporin-A in vincristine and doxorubicin-selected multidrug resistant murine leukemic cells.
2001 Jan
Role of stimulatory guanine nucleotide binding protein (GSalpha) in proliferation of PC-3M prostate cancer cells.
2001 Jan 1
Left ventricular midwall function improves with antihypertensive therapy and regression of left ventricular hypertrophy in patients with asymptomatic hypertension.
2001 Jan 1
Verapamil block of large-conductance Ca-activated K channels in rat aortic myocytes.
2001 Jan 15
In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576.
2001 Jan 15
Behavioural and anti-psychotic effects of Ca2+ channel blockers in rhesus monkey.
2001 Jan 26
Improved intestinal absorption of sulpiride in rats with synchronized oral delivery systems.
2001 Jan 29
Effect of intraovarian factors on porcine follicular cells: cumulus expansion, granulosa and cumulus cell progesterone production.
2001 Jan 31
The effects of LY393613, nimodipine and verapamil, in focal cerebral ischaemia.
2001 Jan 5
Cardiogenic shock following a single therapeutic oral dose of verapamil.
2001 Jan-Feb
Verapamil SR and trandolapril combination therapy is safe and effective in hypertensive patients with metabolic disorders.
2001 Jan-Feb
PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites.
2001 Mar
The effect of cardiac arrest on the blood-testis barrier to albumin, tumor necrosis factor-alpha, pituitary adenylate cyclase activating polypeptide, sucrose, and verapamil in the mouse.
2001 Mar-Apr
Patents

Sample Use Guides

Angina: Clinical trials show that the usual dose is 80 mg to 120 mg three times a day.
Route of Administration: Other
Blockade of L-type calcium channels by verapamil (50 um) prevented a Norgestrel-induced calcium influx in stressed 661W photoreceptor-like cells.
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:27:54 UTC 2021
Edited
by admin
on Sat Jun 26 03:27:54 UTC 2021
Record UNII
CJ0O37KU29
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VERAPAMIL
INN   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
VERAPAMIL SLOW RELEASE
Common Name English
VERAPAMIL [WHO-DD]
Common Name English
VERAPAMIL [USAN]
Common Name English
NSC-272306NA
Code English
D-365
Code English
VERAPAMIL [VANDF]
Common Name English
CP-165331
Code English
CP-16,533-1
Code English
VERAPAMIL [INN]
Common Name English
VERAPAMIL [MI]
Common Name English
(+/-)-5-((3,4-DIMETHOXYPHENETHYL)METHYLAMINO)-2-(3,4-DIMETHOXYPHENYL)-2-ISOPROPYLVALERONITRILE
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000175566
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
WHO-VATC QC09BB10
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
WHO-VATC QC08DA01
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
WHO-ATC C08DA51
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
NCI_THESAURUS C333
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 12.2
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 12.1
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
WHO-VATC QC08DA51
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
NDF-RT N0000000069
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
WHO-ATC C09BB10
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
LIVERTOX 1026
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
WHO-ATC C08DA01
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
Code System Code Type Description
ECHA (EC/EINECS)
200-145-1
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
PUBCHEM
2520
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
IUPHAR
2406
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
INN
2122
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
NDF-RT
N0000182141
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
RXCUI
11170
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY RxNorm
CAS
52-53-9
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
WIKIPEDIA
VERAPAMIL
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
LACTMED
Verapamil
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
DRUG BANK
DB00661
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
MESH
D014700
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
DRUG CENTRAL
2815
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
NDF-RT
N0000185503
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY P-Glycoprotein Inhibitors [MoA]
NCI_THESAURUS
C928
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
FDA UNII
CJ0O37KU29
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
MERCK INDEX
M11414
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY Merck Index
EPA CompTox
52-53-9
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
EVMPD
SUB00038MIG
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
ChEMBL
CHEMBL6966
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY
NDF-RT
N0000190114
Created by admin on Sat Jun 26 03:27:54 UTC 2021 , Edited by admin on Sat Jun 26 03:27:54 UTC 2021
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
IC50
METABOLIC ENZYME -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
22% 0f dose
MAJOR
URINE
METABOLITE ACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
3-4% of dose
MINOR
URINE
METABOLITE -> PARENT
3-4% of dose
MINOR
URINE
METABOLITE -> PARENT
7% of dose
URINE
METABOLITE -> PARENT
6% of dose
MINOR
URINE
METABOLITE ACTIVE -> PARENT
6% of dose
MINOR
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC Populations
PHARMACOKINETIC
Duration of Action PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC Populations
PHARMACOKINETIC
Duration of Action PHARMACOKINETIC