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Details

Stereochemistry RACEMIC
Molecular Formula C27H38N2O4
Molecular Weight 454.6016
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VERAPAMIL

SMILES

COC1=CC=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC=C(OC)C(OC)=C2)C=C1OC

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 454.6016
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description

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

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
[Demonstration of a major preexcitation syndrome during treatment of auricular flutter using intravenous injection of verapamil].
1975
[Mapping electrocardiographic fields in heart hypertrophy].
1998
Effects of the calcium antagonists verapamil and nitrendipine on carbamazepine withdrawal.
1999 Dec
Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil.
1999 Sep
Complete atrioventricular blockade secondary to conventional-release verapamil in a patient on hemodialysis.
1999 Sep
Sleep attacks and Parkinson's disease treatment.
2000 Apr 15
Characterisation of multidrug-resistant Ehrlich ascites tumour cells selected in vivo for resistance to etoposide.
2000 Aug 1
Rhabdomyolysis and acute renal failure in a cardiac transplant recipient due to multiple drug interactions.
2000 Dec
Antiproteinuric effect of calcium antagonists on puromycin-induced experimental nephrosis.
2000 Jan
Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappaB activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis.
2000 Jan 21
Role of the beta(3)-adrenoceptor in urine storage in the rat: comparison between the selective beta(3)-adrenoceptor agonist, CL316, 243, and various smooth muscle relaxants.
2000 Jun
KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels.
2000 Jun
Acute onset of auditory hallucinations after initiation of celecoxib therapy.
2000 Jun
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
Effect of metoprolol and verapamil administered separately and concurrently after single doses on liver blood flow and drug disposition.
2000 May
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
[Treatment of cluster headache].
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
Model organisms: new insights into ion channel and transporter function. L-type calcium channels regulate epithelial fluid transport in Drosophila melanogaster.
2001 Feb
Idiopathic sustained left ventricular tachycardia in pediatric patients.
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
Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia.
2001 Feb
Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells.
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
Multidrug resistance protein (MRP) activity in normal mature leukocytes and CD34-positive hematopoietic cells from peripheral blood.
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
The effects of vasopressin in isolated rat hearts.
2001 Jan
A new chronotherapeutic oral drug absorption system for verapamil optimizes blood pressure control in the morning.
2001 Jan
Effects of simultaneous atrioventricular pacing on atrial refractoriness and atrial fibrillation inducibility: role of atrial mechanoelectrical feedback.
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
Sarcoglycan, the heart, and skeletal muscles: new treatment, old drug?
2001 Jan
Calcium channel blockade limits cardiac remodeling and improves cardiac function in myocardial infarction-induced heart failure in rats.
2001 Jan
Calcium channel antagonists enhance retention of passive avoidance and maze learning in mice.
2001 Jan
A novel zidovudine uptake system in microglia.
2001 Jan
Hepatic uptake of synthetic chlorogenic acid derivatives by the organic anion transport proteins.
2001 Jan
Evaluation of a vincristine resistant Caco-2 cell line for use in a calcein AM extrusion screening assay for P-glycoprotein interaction.
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
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
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

In Vivo Use Guide
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: oral tablets or intravenous injection
In Vitro Use Guide
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 Tue Oct 22 00:47:31 UTC 2019
Edited
by admin
on Tue Oct 22 00:47:31 UTC 2019
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 Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
WHO-VATC QC09BB10
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
WHO-VATC QC08DA01
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
WHO-ATC C08DA51
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
NCI_THESAURUS C333
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 12.2
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 12.1
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
WHO-VATC QC08DA51
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
NDF-RT N0000000069
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
WHO-ATC C09BB10
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
LIVERTOX 1026
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
WHO-ATC C08DA01
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
Code System Code Type Description
ECHA (EC/EINECS)
200-145-1
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
PUBCHEM
2520
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
IUPHAR
2406
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
LactMed
52-53-9
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
INN
2122
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
NDF-RT
N0000182141
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
RXCUI
11170
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY RxNorm
CAS
52-53-9
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
WIKIPEDIA
VERAPAMIL
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
DRUG BANK
DB00661
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
MESH
D014700
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
NDF-RT
N0000185503
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY P-Glycoprotein Inhibitors [MoA]
NCI_THESAURUS
C928
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
MERCK INDEX
M11414
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY Merck Index
EPA CompTox
52-53-9
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
EVMPD
SUB00038MIG
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
ChEMBL
CHEMBL6966
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY
NDF-RT
N0000190114
Created by admin on Tue Oct 22 00:47:31 UTC 2019 , Edited by admin on Tue Oct 22 00:47:31 UTC 2019
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
BINDER->LIGAND
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
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