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 91 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 8228		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 8228

Conditions

Condition	Modality	Highest Phase	Product
Angina 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018925s008lbl.pdf	Primary	Approved 8360	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
Arrhythmia 37 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018925s008lbl.pdf	Primary	Approved 8360	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
Essential hypertension 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018925s008lbl.pdf	Primary	Approved 8360	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

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 1709 inhibitor 1579	substrate 1010 inhibitor 1752	inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 506	CYP1A2 1032 CYP2C8 688 CYP2C18 139

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 146.0	likely
CYP3A4 1909	inhibitor 3240 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 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 99.0	weak
OCT1 523	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 1.23 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	yes
CYP2C18 139	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	yes
CYP2C8 688	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	yes
CYP2C9 1010	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019152s044lbl.pdf#page=7 Page: 7.0	yes
CYP3A4 1709	substrate 3326 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 1632	inhibitor 1613 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
[Asystole followed by cardiogenic shock after intravenous injection of verapamil].	1975 Mar-Apr	1094900
Increase in doxorubicin cytotoxicity by carvedilol inhibition of P-glycoprotein activity.	1999 Dec 1	10571255
Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice.	1999 Feb	10368871
Comparison of intravenous metoprolol, verapamil and diltiazem on the attenuation of haemodynamic changes associated with tracheal extubation.	1999 Jul	10457878
[Verapamil sensitive ventricular tachycardia with myocardial failure in a 2-year-old child].	1999 May	10413860
P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil.	1999 Oct	10527640
Complete atrioventricular blockade secondary to conventional-release verapamil in a patient on hemodialysis.	1999 Sep	10461042
Sleep attacks and Parkinson's disease treatment.	2000 Apr 15	10776750
Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers.	2000 Feb	11218825
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	10869395
Transition-state formation in ATPase-negative mutants of human MDR1 protein.	2000 Oct 5	11027628
Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment.	2001 Feb	11234888
[Treatment of cluster headache].	2001 Feb	11234673
Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats.	2001 Feb	11231107
Oxidized-LDL enhances coronary vasoconstriction by increasing the activity of protein kinase C isoforms alpha and epsilon.	2001 Feb	11230335
Refractory no-reflow successfully treated with local infusion of high-dose adenosine and verapamil--a case report.	2001 Feb	11228087
Idiopathic sustained left ventricular tachycardia in pediatric patients.	2001 Feb	11207998
Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone.	2001 Feb	11159804
Ivermectin excretion by isolated functionally intact brain endothelial capillaries.	2001 Feb	11159725
Multidrug resistance protein (MRP) activity in normal mature leukocytes and CD34-positive hematopoietic cells from peripheral blood.	2001 Feb 2	11233999
Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats.	2001 Feb 2	11166291
Cardiovascular action of a cardioselective Ca(2+)channel blocker AH-1058 in conscious dogs assessed by telemetry.	2001 Feb 9	11173068
Identification of an organic anion transport system in the human colon carcinoma cell line HT29 clone 19A.	2001 Jan	11212217
Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex.	2001 Jan	11160141
Sarcoglycan, the heart, and skeletal muscles: new treatment, old drug?	2001 Jan	11160128
Left ventricular midwall function improves with antihypertensive therapy and regression of left ventricular hypertrophy in patients with asymptomatic hypertension.	2001 Jan 1	11137835
Behavioural and anti-psychotic effects of Ca2+ channel blockers in rhesus monkey.	2001 Jan 26	11165225
Cardiogenic shock following a single therapeutic oral dose of verapamil.	2001 Jan-Feb	11219325
Verapamil SR and trandolapril combination therapy is safe and effective in hypertensive patients with metabolic disorders.	2001 Jan-Feb	11219319
PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites.	2001 Mar	11181501
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	11121420
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	11229799

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 `Thu Jul 06 23:03:16 UTC 2023` Edited by `admin` on `Thu Jul 06 23:03:16 UTC 2023`
Record UNII	CJ0O37KU29
Record Status	`Validated (UNII)`
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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