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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:: As a lipophilic substance, verapamil easily crosses the blood–brain barrier. Verapamil is, however, a substrate for the efflux transporter P-glycoprotein (P-gp) in the blood–brain barrier. The P-pg restricts net brain uptake of verapamil by immediately transporting 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

3.66336016E11
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

3.66336016E11
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

3.66336016E11
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 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: 7.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Asystole followed by cardiogenic shock after intravenous injection of verapamil].
1975 Mar-Apr
[Mapping electrocardiographic fields in heart hypertrophy].
1998
[The importance of the ion-transport systems of the sarcolemma and sarcoplasmic reticulum in changing rat cardiac contractile function under a hypersodium medium].
1999 Apr
Effects of the calcium antagonists verapamil and nitrendipine on carbamazepine withdrawal.
1999 Dec
Neurological recovery after prolonged verapamil-induced cardiac arrest.
1999 Dec
Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites.
2000 Apr
Characterisation of multidrug-resistant Ehrlich ascites tumour cells selected in vivo for resistance to etoposide.
2000 Aug 1
Sensitivity of native and cloned hippocampal delayed-rectifier potassium channels to verapamil.
2000 Jan 4
Antiarrhythmic and cardiohemodynamic effects of a novel Ca(2+) channel blocker, AH-1058, assessed in canine arrhythmia models.
2000 Jun 9
Early administration of verapamil after thrombolysis in acute anterior myocardial infarction. Effect on left ventricular remodeling and clinical outcome. VAMI Study Group. Verapamil Acute Myocardial Infarction.
2000 May
Increased incidence of infection in verapamil-treated kidney transplant recipients.
2000 May
Attenuation of changes in sarcoplasmic reticular gene expression in cardiac hypertrophy by propranolol and verapamil.
2000 Oct
Dimeric 4-aryl-1,4-dihydropyridines as novel HIV-1 protease inhibitors--affinities to intestinal P-glycoprotein.
2000 Oct
Transition-state formation in ATPase-negative mutants of human MDR1 protein.
2000 Oct 5
Monitoring of cellular resistance to cancer chemotherapy: drug retention and efflux.
2001
Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment.
2001 Feb
Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats.
2001 Feb
Oxidized-LDL enhances coronary vasoconstriction by increasing the activity of protein kinase C isoforms alpha and epsilon.
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
A bioreversible prodrug approach designed to shift mechanism of brain uptake for amino-acid-containing anticancer agents.
2001 Feb
Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia.
2001 Feb
Ivermectin excretion by isolated functionally intact brain endothelial capillaries.
2001 Feb
Infusional CHOP chemotherapy (CVAD) with or without chemosensitizers offers no advantage over standard CHOP therapy in the treatment of lymphoma: a Southwest Oncology Group Study.
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
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
Identification of an organic anion transport system in the human colon carcinoma cell line HT29 clone 19A.
2001 Jan
Penetration of verapamil hydrochloride in the presence of sodium glycocholate as penetration enhancer through mucous membrane.
2001 Jan
Verapamil prevents stretch-induced shortening of atrial effective refractory period in langendorff-perfused rabbit heart.
2001 Jan
Ionized magnesium in the homeostasis of cells: intracellular threshold for Mg(2+) in human platelets.
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
P-glycoprotein-mediated drug secretion in mouse proximal tubule perfused in vitro.
2001 Jan
Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris.
2001 Jan
Calcium channel antagonists enhance retention of passive avoidance and maze learning in mice.
2001 Jan
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
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
Requirement of neural activity for the maintenance of dopaminergic neurons in rat midbrain slice cultures.
2001 Mar 16
Correlation between steady-state ATP hydrolysis and vanadate-induced ADP trapping in Human P-glycoprotein. Evidence for ADP release as the rate-limiting step in the catalytic cycle and its modulation by substrates.
2001 Mar 23
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. However, 40 mg three times a day may be warranted in patients who may have an increased response to verapamil (eg, decreased hepatic function, elderly, etc). Upward titration should be based on therapeutic efficacy and safety evaluated approximately eight hours after dosing. Dosage may be increased at daily (eg, patients with unstable angina) or weekly intervals until optimum clinical response is obtained. Arrhythmias: The dosage in digitalized patients with chronic atrial fibrillation (see PRECAUTIONS) ranges from 240 to 320 mg/day in divided (t.i.d. or q.i.d.) doses. The dosage for prophylaxis of PSVT (non-digitalized patients) ranges from 240 to 480 mg/day in divided (t.i.d. or q.i.d.) doses. In general, maximum effects for any given dosage will be apparent during the first 48 hours of therapy. Essential hypertension: Dose should be individualized by titration. The usual initial monotherapy dose in clinical trials was 80 mg three times a day (240 mg/day). Daily dosages of 360 and 480 mg have been used but there is no evidence that dosages beyond 360 mg provided added effect. Consideration should be given to beginning titration at 40 mg three times per day in patients who might respond to lower doses, such as the elderly or people of small stature. The antihypertensive effects of CALAN are evident within the first week of therapy. Upward titration should be based on therapeutic efficacy, assessed at the end of the dosing interval.
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]
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