VERAPAMIL

First approved in 1978

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 Search

SMILES

COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1

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	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018817s032lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel 92 Target ID: CHEMBL2095229 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018817s027lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/27856310 \| https://www.ncbi.nlm.nih.gov/pubmed/19125880	Inhibitor 8297		3.4 µM [IC50]
Voltage-gated L-type calcium channel alpha-1C subunit 44 Target ID: CHEMBL1940 Sources: https://www.drugbank.ca/drugs/DB00661 \| https://www.ncbi.nlm.nih.gov/pubmed/15880143	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Angina 32 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018925s008lbl.pdf	Primary	Approved 8429	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 1981
Arrhythmia 38 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018925s008lbl.pdf	Primary	Approved 8429	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 1981
Essential hypertension 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018925s008lbl.pdf	Primary	Approved 8429	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 1981

C_max

Value	Dose	Co-administered	Analyte	Population
139.28 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16892180	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

Value	Dose	Co-administered	Analyte	Population
367.05 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16892180	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.15 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16892180	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
9.9% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6209501			VERAPAMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 512	CYP1A2 1054 CYP2C8 693 CYP2C18 138

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 146.0	likely
CYP3A4 1925	inhibitor 3277 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.2001.01386.x#page=1 Page: 1.0	moderate [IC50 23 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 99.0	weak
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 1.23 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	yes
CYP2C18 138	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	yes
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/10325236/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY526351	https://www.001chemical.com/chem/152-11-4
001 Chemical	DY558136	https://www.001chemical.com/chem/52-53-9
3B Scientific (Wuhan) Corp	3B2-0664	http://www.3bsc.com/index/pro_info.php?id=20020
AHH Chemical co.,ltd	API-1634	http://www.ahhchemical.com/product/API-1634.html
Achemtek	0104-013440	http://www.achemtek.com/52-53-9
Alsachim	4116	http://www.alsachim.com/product-C5426-glo.bal-view.html
Ambeed	A149080	https://www.ambeed.com/products/52-53-9.html
AvaChem Scientific	4687B	http://www.avachem.com/productSearch.asp?4687B
Avantor Inc	101097-322	https://us.vwr.com/store/catalog/product.jsp?catalog_number=101097-322
BLD Pharm	BD156394	http://www.bldpharm.com/products/52-53-9.html
BroadPharm	BP-21223	http://www.broadpharm.com/web/product.php?catalog=BP-21223
CSNpharm	CSN25647	https://www.csnpharm.com/products/verapamil.html
Chem Scene	CS-0002967	http://www.chemscene.com/52-53-9.html
ChemMol	30105063	http://www.chemmol.com/chemmol/30105063.html
ChemMol	49417199	http://www.chemmol.com/chemmol/49417199.html
ChemMol	99097786	http://www.chemmol.com/chemmol/99097786.html
Chemspace	CSSB00000051941	https://chem-space.com/CSSB00000051941
Clearsynth	CS-O-30814	https://www.clearsynth.com/en/CSO30814.html
DC Chemicals	DC7880	http://www.dcchemicals.com/product_show-CP_16533_1_Verapamil_.html
Finetech	FT-0675801	http://www.finetechnology-ind.com/prod/detail/pub/36622-29-4.html
Finetech	FT-0603225	http://www.finetechnology-ind.com/prod/detail/pub/52-53-9.html
Hairui	HR137435	http://www.hairuichem.com/en/product/52-53-9.html
Lab Network	LN01346584	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01346584
MedChem Express	HY-14275	https://www.medchemexpress.com/verapamil.html
Molcore	MC526351	https://www.molcore.com/product/152-11-4
Molcore	MC558136	https://www.molcore.com/product/52-53-9
OChem	5898	http://www.ocheminc.com/index.php?act=psearch&pid=52V114
Parchem	18406	http://www.parchem.com/chemical-supplier-distributor/Linoleamidopropyl-PG-Dimonium-Chloride-Phosphate-008406.aspx
Parchem	30276	http://www.parchem.com/chemical-supplier-distributor/Verapamil-020276.aspx
Smolecule	S546686	http://www.smolecule.com/products/s546686
THE BioTek	bt-285978	https://www.thebiotek.com/product/inhibitors/bt-285978
eNovation Chemicals	K22170	https://www.enovationchem.com/ProductDetails.asp?ProductID=K22170
iChemical	EBD29756	http://www.ichemical.com/chemicals/cas-52-53-9
mcule	MCULE-3016077278	https://mcule.com/MCULE-3016077278/

PubMed

Title	Date	PubMed
[Demonstration of a major preexcitation syndrome during treatment of auricular flutter using intravenous injection of verapamil].	1975	1079999
[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	10513388
Neurological recovery after prolonged verapamil-induced cardiac arrest.	1999 Dec	10631424
Successful resuscitation of a verapamil-intoxicated patient with percutaneous cardiopulmonary bypass.	1999 Dec	10628632
P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil.	1999 Oct	10527640
Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil.	1999 Sep	10511059
Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers.	2000 Feb	11218825
Acute onset of auditory hallucinations after initiation of celecoxib therapy.	2000 Jun	10831492
Antiarrhythmic and cardiohemodynamic effects of a novel Ca(2+) channel blocker, AH-1058, assessed in canine arrhythmia models.	2000 Jun 9	10856454
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	10832809
Attenuation of changes in sarcoplasmic reticular gene expression in cardiac hypertrophy by propranolol and verapamil.	2000 Oct	11129949
[Treatment of cluster headache].	2001 Feb	11234673
Inward calcium currents in cultured and freshly isolated detrusor muscle cells: evidence of a T-type calcium current.	2001 Feb	11176448
Intra- and intercellular Ca(2+)-transient propagation in normal and high glucose solutions in ROS cells during mechanical stimulation.	2001 Feb	11162851
L-type calcium channel blockers and EGTA enhance superoxide production in cardiac fibroblasts.	2001 Feb	11162140
Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia.	2001 Feb	11160647
Signaling mechanisms for the selective vasoconstrictor effect of norbormide on the rat small arteries.	2001 Feb	11160631
Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells.	2001 Feb	11160630
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	11160625
Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone.	2001 Feb	11159804
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	11157027
hKv4.3 channel characterization and regulation by calcium channel antagonists.	2001 Feb 23	11181069
Calcium channel blockade limits cardiac remodeling and improves cardiac function in myocardial infarction-induced heart failure in rats.	2001 Jan	11152376
P-glycoprotein-mediated drug secretion in mouse proximal tubule perfused in vitro.	2001 Jan	11134265
Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris.	2001 Jan	11133211
Competitive and allosteric interactions in ligand binding to P-glycoprotein as observed on an immobilized P-glycoprotein liquid chromatographic stationary phase.	2001 Jan	11125025
In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576.	2001 Jan 15	11212278
Suppression by verapamil of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in wistar rats.	2001 Jan-Feb	11125235

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: Other

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 `Sat Dec 16 17:42:15 GMT 2023` Edited by `admin` on `Sat Dec 16 17:42:15 GMT 2023`
Record UNII	CJ0O37KU29
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VERAPAMIL

Official Name

English

VERAPAMIL SLOW RELEASE

Common Name

English

VERAPAMIL [USAN]

Common Name

English

D-365

Code

English

Verapamil [WHO-DD]

Common Name

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