Verapamil is a phenylalkylamine calcium channel blocker used in the treatment of high blood pressure, heart arrhythmias, and angina,¹⁶ and was the first calcium channel antagonist to be introduced into therapy in the early 1960s.¹³ It is a member of the non-dihydropyridine class of calcium channel blockers, which includes drugs like diltiazem and flunarizine, but is chemically unrelated to other cardioactive medications.¹⁶ Verapamil is administered as a racemic mixture containing equal amounts of the S- and R-enantiomer, each of which is pharmacologically distinct - the S-enantiomer carries approximately 20-fold greater potency than the R-enantiomer, but is metabolized at a higher rate.⁵

Structure

Similar Structures

Synonyms

Iproveratril
Vérapamil
Verapamil
Verapamilo
Verapamilum

External IDs

CP-16,533-1 / D-365

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Verapamil hydrochloride	V3888OEY5R	152-11-4	DOQPXTMNIUCOSY-UHFFFAOYSA-N

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Calan	Tablet, film coated	120 mg/1	Oral	Physicians Total Care, Inc.	1994-07-05	2012-06-30
Calan	Tablet, film coated	120 mg/1	Oral	G.D. Searle LLC Division of Pfizer Inc	1984-09-10	Not applicable
Calan	Tablet, film coated	40 mg/1	Oral	G.D. Searle LLC	2006-06-01	2006-06-01
Calan	Tablet, film coated	80 mg/1	Oral	G.D. Searle LLC Division of Pfizer Inc	1984-09-10	2018-06-30
Calan SR	Tablet, film coated, extended release	180 mg/1	Oral	G.D. Searle LLC Division of Pfizer Inc	1989-12-15	Not applicable
Calan SR	Tablet, film coated, extended release	120 mg/1	Oral	G.D. Searle LLC Division of Pfizer Inc	1991-03-06	Not applicable
Calan SR	Tablet, film coated, extended release	180 mg/1	Oral	Physicians Total Care, Inc.	1992-11-17	2012-06-30
Calan SR	Tablet, film coated, extended release	120 mg/1	Oral	Physicians Total Care, Inc.	1994-07-25	2012-06-30
Calan SR	Tablet, film coated, extended release	240 mg/1	Oral	G.D. Searle LLC Division of Pfizer Inc	1986-12-16	Not applicable
Covera-HS	Tablet, extended release	240 mg	Oral	Pfizer Canada Ulc	1997-11-13	2013-02-15

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products

Name	Dosage	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Alti-verapamil - 120mg	Tablet	Oral	Altimed Pharma Inc.	1990-12-31	2004-08-03
Alti-verapamil - 80mg	Tablet	Oral	Altimed Pharma Inc.	1990-12-31	2004-08-03
Apo-verap SR	Tablet, extended release	Oral	Apotex Corporation	2003-04-24	Not applicable
Apo-verap SR	Tablet, extended release	Oral	Apotex Corporation	2003-04-24	Not applicable
Apo-verap SR	Tablet, extended release	Oral	Apotex Corporation	2003-04-24	Not applicable
Apo-verap Tab 80mg	Tablet	Oral	Apotex Corporation	1989-12-31	Not applicable
Apo-verap Tablet 120mg	Tablet	Oral	Apotex Corporation	1989-12-31	Not applicable
Dom-verapamil SR 240mg Tablets	Tablet, extended release	Oral	Dominion Pharmacal	1999-12-16	Not applicable
Med Verapamil Tablets	Tablet	Oral	Medican Pharma Incorporated	1999-03-08	2011-03-29
Med Verapamil Tablets	Tablet	Oral	Medican Pharma Incorporated	1999-03-08	2011-03-29

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Product Code

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Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Tarka	Verapamil hydrochloride (240 mg/1) + Trandolapril (1 mg/1)	Tablet, film coated, extended release	Oral	AbbVie Inc.	1996-10-22	2018-02-28
Tarka	Verapamil hydrochloride (180 mg) + Trandolapril (2 mg)	Tablet, extended release	Oral	Abbott	2002-07-15	2010-11-12
Tarka	Verapamil hydrochloride (240 mg) + Trandolapril (4 mg)	Tablet, extended release	Oral	Bgp Pharma Ulc	2002-07-15	2019-11-19
Tarka	Verapamil hydrochloride (180 mg/1) + Trandolapril (2 mg/1)	Tablet, film coated, extended release	Oral	AbbVie Inc.	1996-10-22	2021-08-14
Tarka	Verapamil hydrochloride (240 mg/1) + Trandolapril (4 mg/1)	Tablet, film coated, extended release	Oral	Physicians Total Care, Inc.	2009-06-25	Not applicable
Tarka	Verapamil hydrochloride (240 mg/1) + Trandolapril (2 mg/1)	Tablet, film coated, extended release	Oral	Physicians Total Care, Inc.	2005-05-27	Not applicable
Tarka	Verapamil hydrochloride (240 mg/1) + Trandolapril (4 mg/1)	Tablet, film coated, extended release	Oral	AbbVie Inc.	1996-10-22	2021-08-18
Tarka	Verapamil hydrochloride (240 mg) + Trandolapril (2 mg)	Tablet, extended release	Oral	Bgp Pharma Ulc	2002-07-15	2019-11-19
Tarka	Verapamil hydrochloride (180 mg/1) + Trandolapril (2 mg/1)	Tablet, film coated, extended release	Oral	Physicians Total Care, Inc.	2009-01-01	Not applicable
Tarka	Verapamil hydrochloride (240 mg) + Trandolapril (1 mg)	Tablet, extended release	Oral	Abbott	2002-07-15	2010-11-12

International/Other Brands

Bosoptin (Bosnalijek) / Isoptin (Abbott) / Verisop (Gerard) / Vermin (Ratiopharm) / Vermine (Pharmasant) / Verogalid (Ivax) / Verogalid ER (Ivax) / Verpamil (Mylan) / Vertab (Trinity-Chiesi) / Vetrimil (CCPC) / Zolvera (Rosemont)

Categories

UNII

CJ0O37KU29

CAS number

52-53-9

Weight

Average: 454.6016
Monoisotopic: 454.283157714

Chemical Formula

C₂₇H₃₈N₂O₄

InChI Key

SGTNSNPWRIOYBX-UHFFFAOYSA-N

InChI

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

IUPAC Name

2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile

SMILES

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

Pharmacology

Indication

Verapamil is indicated in the treatment of vasopastic (i.e. Prinzmetal's) angina, unstable angina, and chronic stable angina. It is also indicated to treat hypertension, for the prophylaxis of repetitive paroxysmal supraventricular tachycardia, and in combination with digoxin to control ventricular rate in patients with atrial fibrillation or atrial flutter.¹⁶ Given intravenously, it is indicated for the treatment of various supraventricular tachyarrhythmias, including rapid conversion to sinus rhythm in patients with supraventricular tachycardia and for temporary control of ventricular rate in patients with atrial fibrillation or atrial flutter.¹⁵

Verapamil is commonly used off-label for prophylaxis of cluster headaches.⁴

Associated Conditions

Pharmacodynamics

Verapamil is an L-type calcium channel blocker with antiarrhythmic, antianginal, and antihypertensive activity.¹⁶ Immediate-release verapamil has a relatively short duration of action, requiring dosing 3 to 4 times daily,¹⁶ but extended-release formulations are available that allow for once-daily dosing.^14,19 As verapamil is a negative inotropic medication (i.e. it decreases the strength of myocardial contraction), it should not be used in patients with severe left ventricular dysfunction or hypertrophic cardiomyopathy as the decrease in contractility caused by verapamil may increase the risk of exacerbating these pre-existing conditions.¹⁴

Mechanism of action

Verapamil inhibits L-type calcium channels by binding to a specific area of their alpha-1 subunit¹⁴ - Cav1.2, the predominant L-type calcium channel in the cardiovascular system, is found in vascular smooth muscle and myocardial tissue and is responsible for control of peripheral vascular resistance and heart contractility.¹⁰ Calcium influx through these channels allows for the propagation of action potentials necessary for the contraction of muscle tissue and the heart's electrical pacemaker activity. Verapamil binds to these channels in a voltage- and frequency-dependent manner, meaning affinity is increased 1) as vascular smooth muscle membrane potential is reduced, and 2) with excessive depolarizing stimulus.¹⁴

Verapamil's mechanism of action in the treatment of angina and hypertension is largely the same. Inhibition of calcium influx prevents the contraction of vascular smooth muscle, causing relaxation/dilation of blood vessels throughout the peripheral circulation - this lowers systemic vascular resistance (i.e. afterload) and thus blood pressure. This reduction in vascular resistance also reduces the force against which the heart must push, decreasing myocardial energy consumption and oxygen requirements and thus alleviating angina.¹⁶

Electrical activity through the AV node is responsible for determining heart rate, and this activity is dependent upon calcium influx through L-type calcium channels. By inhibiting these channels and decreasing the influx of calcium, verapamil prolongs the refractory period of the AV node and slows conduction, thereby slowing and controlling the heart rate in patients with arrhythmia.¹⁶

Verapamil's mechanism of action in the treatment of cluster headaches is unclear, but is thought to result from an effect on other calcium channels (e.g. N-, P-, Q-, or T-type).⁴

Verapamil is known to interact with other targets, including other calcium channels,^7,8 potassium channels,^6,4 and adrenergic receptors.^11,12

Target	Actions	Organism
AVoltage-dependent L-type calcium channel subunit alpha-1C	inhibitor	Humans
UVoltage-dependent N-type calcium channel subunit alpha-1B	inhibitor	Humans
UVoltage-dependent P/Q-type calcium channel subunit alpha-1A	inhibitor	Humans
UATP-sensitive inward rectifier potassium channel 11	inhibitor	Humans
UVoltage-dependent T-type calcium channel subunit alpha-1G	inhibitor	Humans
UVoltage-dependent T-type calcium channel subunit alpha-1H	inhibitor	Humans
UPotassium voltage-gated channel subfamily H member 2	inhibitor	Humans
USodium-dependent serotonin transporter	unknown	Humans
UAlpha-1A adrenergic receptor	antagonist	Humans
UAlpha-1B adrenergic receptor	antagonist	Humans
UAlpha-1D adrenergic receptor	antagonist	Humans

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Adverse Effects

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Contraindications

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Absorption

More than 90% of orally administered verapamil is absorbed - despite this, bioavailability ranges only from 20% to 30% due to rapid biotransformation following first-pass metabolism in the portal circulation.¹⁶ Absorption kinetic parameters are largely dependent on the specific formulation of verapamil involved. Immediate-release verapamil reaches peak plasma concentrations (i.e. T_max) between 1-2 hours following administration,¹⁶ whereas sustained-release formulations tend to have a T_max between 6 - 11 hours.^14,19

AUC and C_max values are similarly dependent upon formulation. Chronic administration of immediate-release verapamil every 6 hours resulted in plasma concentrations between 125 and 400 ng/mL.¹⁶ Steady-state AUC_0-24h and C_max values for a sustained-release formulation were 1037 ng∙h/ml and 77.8 ng/mL for the R-isomer and 195 ng∙h/ml and 16.8 ng/mL for the S-isomer, respectively.¹⁴

Interestingly, the absorption kinetics of verapamil are highly stereospecific - following oral administration of immediate-release verapamil every 8 hours, the relative systemic availability of the S-enantiomer compared to the R-enantiomer was 13% after a single dose and 18% at steady-state.¹⁴

Volume of distribution

Verapamil has a steady-state volume of distribution of approximately 300L for its R-enantiomer and 500L for its S-enantiomer.⁴

Protein binding

Verapamil is extensively protein-bound in plasma. R-verapamil is 94% bound to serum albumin while S-verapamil is 88% bound. Additionally, R-verapamil is 92% bound to alpha-1 acid glycoprotein and S-verapamil is 86% bound.¹⁶

Metabolism

Verapamil is extensively metabolized by the liver, with up to 80% of an administered dose subject to elimination via pre-systemic metabolism - interestingly, this first-pass metabolism appears to clear the S-enantiomer of verapamil much faster than the R-enantiomer.^14,9 The remaining parent drug undergoes O-demethylation, N-dealkylation, and N-demethylation to a number of different metabolites via the cytochrome P450 enzyme system.⁹ Norverapamil, one of the major circulating metabolites, is the result of verapamil's N-demethylation via CYP2C8, CYP3A4, and CYP3A5,⁹ and carries approximately 20% of the cardiovascular activity of its parent drug.¹⁴ The other major pathway involved in verapamil metabolism is N-dealkylation via CYP2C8, CYP3A4, and CYP1A2 to the D-617 metabolite. Both norverapamil and D-617 are further metabolized by other CYP isoenzymes to various secondary metabolites. CYP2D6 and CYP2E1 have also been implicated in the metabolic pathway of verapamil, albeit to a minor extent.⁹ Minor pathways of verapamil metabolism involve its O-demethylation to D-703 via CYP2C8, CYP2C9, and CYP2C18, and to D-702 via CYP2C9 and CYP2C18.⁹

Several steps in verapamil's metabolic pathway show stereoselective preference for the S-enantiomer of the given substrate, including the generation of the D-620 metabolite by CYP3A4/5 and the D-617 metabolite by CYP2C8.⁹

Route of elimination

Approximately 70% of an administered dose is excreted as metabolites in the urine and ≥16% in the feces within 5 days. Approximately 3% - 4% is excreted in the urine as unchanged drug.¹⁶

Half life

Single-dose studies of immediate-release verapamil have demonstrated an elimination half-life of 2.8 to 7.4 hours, which increases to 4.5 to 12.0 hours following repetitive dosing.¹⁶ The elimination half-life is also prolonged in patients with hepatic insufficiency (14 to 16 hours) and in the elderly (approximately 20 hours).¹⁴ Intravenously administered verapamil has rapid distribution phase half-life of approximately 4 minutes, followed by a terminal elimination phase half-life of 2 to 5 hours.¹⁵

Clearance

Systemic clearance following 3 weeks of continuous treatment was approximately 340 mL/min for R-verapamil and 664 mL/min for S-verapamil.⁵ Of note, apparent oral clearance appears to vary significantly between single dose and multiple-dose conditions. The apparent oral clearance following single doses of verapamil was approximately 1007 mL/min for R-verapamil and 5481 mL/min for S-verapamil, whereas 3 weeks of continuous treatment resulted in apparent oral clearance values of approximately 651 mL/min for R-verapamil and 2855 mL/min for S-verapamil.⁵

Toxicity

Verapamil's reported oral TDLo is 14.4 mg/kg in women and 3.429 mg/kg in men.¹⁸ The oral LD₅₀ is 150 mg/kg in rats and 163 mg/kg in mice.¹⁸

As there is no antidote for verapamil overdosage, treatment is largely supportive. Symptoms of overdose are generally consistent with verapamil's adverse effect profile (i.e. hypotension, bradycardia, arrhythmia) but instances of non-cardiogenic pulmonary edema have been observed following ingestion of large overdoses (up to 9 grams).¹⁴ In acute overdosage, consider the use of gastrointestinal decontamination with cathartics and/or bowel irrigation. Patients presenting with significant myocardial depression may require intravenous calcium, atropine, vasopressors, or other inotropes. Consider the formulation responsible for the overdose prior to treatment - sustained-release formulations may result in delayed pharmacodynamic effects, and these patients should be monitored closely for at least 48 hours following ingestion.¹⁴

Affected organisms

Humans and other mammals

Pathways

Pathway	Category
Verapamil Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Beta-1 adrenergic receptor	---	(C;G) / (G;G)	G > C	Effect Directly Studied	Patients with this genotype require a lower dosage of verapamil to achieve a favourable rate-control response when treating atrial fibrillation.	Details

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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(R)-warfarin	The serum concentration of (R)-warfarin can be increased when it is combined with Verapamil.
(S)-Warfarin	The serum concentration of (S)-Warfarin can be increased when it is combined with Verapamil.
2,4-thiazolidinedione	The risk or severity of hypoglycemia can be increased when Verapamil is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine	The therapeutic efficacy of Verapamil can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine	The therapeutic efficacy of Verapamil can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	The therapeutic efficacy of Verapamil can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-Bromo-2,5-dimethoxyphenethylamine	The therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Verapamil.
4-hydroxycoumarin	The metabolism of 4-hydroxycoumarin can be decreased when combined with Verapamil.
4-Methoxyamphetamine	The therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Verapamil.
5-methoxy-N,N-dimethyltryptamine	The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Verapamil.

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Food Interactions

Avoid alcohol.
Avoid excessive quantities of coffee or tea (Caffeine).
Avoid natural licorice.
Avoid taking with grapefruit juice.
Take with food.

References

Synthesis Reference

Philippe Baudier, Arthur De Boeck, Jacques Fossion, "Novel galenic forms of verapamil, their preparation and medicines containing said novel galenic forms." U.S. Patent US4859469, issued April, 1987.

US4859469

General References

Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83. [PubMed:8725386]
Ahmed JH, Meredith PA, Elliott HL: The influence of age on the pharmacokinetics of verapamil. Pharmacol Res. 1991 Oct;24(3):227-33. doi: 10.1016/1043-6618(91)90085-c. [PubMed:1956867]
Dadashzadeh S, Javadian B, Sadeghian S: The effect of gender on the pharmacokinetics of verapamil and norverapamil in human. Biopharm Drug Dispos. 2006 Oct;27(7):329-34. doi: 10.1002/bdd.512. [PubMed:16892180]
Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [PubMed:19125880]
Busse D, Fromm MF, Morike K, Drescher S, Kuhlkamp V, Eichelbaum M: Disposition and pharmacologic effects of R/S-verapamil in patients with chronic atrial fibrillation: an investigation comparing single and multiple dosing. Clin Pharmacol Ther. 2001 May;69(5):324-32. doi: 10.1067/mcp.2001.115125. [PubMed:11372000]
Ninomiya T, Takano M, Haruna T, Kono Y, Horie M: Verapamil, a Ca2+ entry blocker, targets the pore-forming subunit of cardiac type KATP channel (Kir6.2). J Cardiovasc Pharmacol. 2003 Aug;42(2):161-8. doi: 10.1097/00005344-200308000-00002. [PubMed:12883317]
Bergson P, Lipkind G, Lee SP, Duban ME, Hanck DA: Verapamil block of T-type calcium channels. Mol Pharmacol. 2011 Mar;79(3):411-9. doi: 10.1124/mol.110.069492. Epub 2010 Dec 13. [PubMed:21149638]
Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [PubMed:18974361]
Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Striessnig J, Ortner NJ, Pinggera A: Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets? Curr Mol Pharmacol. 2015;8(2):110-22. [PubMed:25966690]
Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [PubMed:9570190]
Motulsky HJ, Snavely MD, Hughes RJ, Insel PA: Interaction of verapamil and other calcium channel blockers with alpha 1- and alpha 2-adrenergic receptors. Circ Res. 1983 Feb;52(2):226-31. [PubMed:6297831]
Echizen H, Eichelbaum M: Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. Clin Pharmacokinet. 1986 Nov-Dec;11(6):425-49. doi: 10.2165/00003088-198611060-00002. [PubMed:3542336]
FDA Approved Drug Products: Verelan® PM extended-release capsules [Link]
FDA Approved Drug Products: Verapamil HCl for intravenous injection [Link]
Verapamil FDA Label [Link]
FDA Approved Drugs: Tarka® extended-release tablets [Link]
CaymanChem: Verapamil MSDS [Link]
FDA Approved Drug Products: Calan SR tablets [Link]

External Links

Human Metabolome Database: HMDB0001850
KEGG Drug: D02356
KEGG Compound: C07188
PubChem Compound: 2520
PubChem Substance: 46508158
ChemSpider: 2425
BindingDB: 81939
ChEBI: 77733
ChEMBL: CHEMBL6966
Therapeutic Targets Database: DAP000040
PharmGKB: PA451868
Guide to Pharmacology: GtP Drug Page
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Verapamil

ATC Codes

C09BB10 — Trandolapril and verapamil

C08DA51 — Verapamil, combinations

C08DA01 — Verapamil

AHFS Codes

24:28.92 — Miscellaneous Calcium-channel Blocking Agents

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Crohn's Disease (CD)	1
1	Completed	Not Available	Healthy Volunteers	5
1	Completed	Not Available	Substance, Addiction	1
1	Completed	Basic Science	Drug Drug Interaction (DDI) / Healthy Volunteers	2
1	Completed	Basic Science	Healthy Volunteers	2
1	Completed	Basic Science	Healthy Volunteers / Pharmacokinetics of ASP015K	1
1	Completed	Basic Science	Opioid Dependence	1
1	Completed	Basic Science	Pharmacokinetics	1
1	Completed	Basic Science	Substance, Addiction	1
1	Completed	Diagnostic	Chronic Subjective Dizziness / Vestibular Migraine	1
1	Completed	Other	Drug-induced QT Interval Prolongation / Pharmacodynamics / Pharmacokinetics	1
1	Completed	Other	Healthy Volunteers	1
1	Completed	Treatment	Drug-induced Surface ECG Changes	1
1	Completed	Treatment	Healthy Adult Subjects	1
1	Completed	Treatment	Healthy Volunteers	4
1	Completed	Treatment	Idiopathic Thrombocytopenic Purpura	1
1	Completed	Treatment	Infections, Respiratory Syncytial Virus	1
1	Completed	Treatment	Stroke, Ischemic	1
1	Completed	Treatment	Type 2 Diabetes Mellitus	1
1	Recruiting	Basic Science	Cardiovascular System Disease / Drug-Related Side Effects and Adverse Reactions	1
1	Recruiting	Treatment	CD30-Positive Neoplastic Cells Present / Recurrent Hodgkin Lymphoma / Refractory Hodgkin Lymphoma	1
1	Recruiting	Treatment	Stroke, Ischemic	2
1	Terminated	Treatment	Polyps, Nasal / Sinusitis	1
1	Withdrawn	Treatment	Stroke, Ischemic	1
1, 2	Completed	Health Services Research	Healthy Volunteers	1
1, 2	Terminated	Treatment	Knee Osteoarthritis (Knee OA)	1
2	Active Not Recruiting	Treatment	Type 1 Diabetes Mellitus	1
2	Completed	Treatment	Brain Cancer / Malignancies / Meningiomas	1
2	Completed	Treatment	Dravet Syndrome	1
2	Terminated	Prevention	Episodic Cluster Headache	1
2	Unknown Status	Diagnostic	Epilepsies	1
2, 3	Completed	Treatment	Cluster Headache	1
2, 3	Recruiting	Treatment	Arrhythmia of ventricular origin	1
3	Completed	Treatment	Arrhythmia / Atrial Fibrillation (AF) / Cardiovascular Heart Disease / Heart Diseases	1
3	Completed	Treatment	Atrial Fibrillation (AF)	1
3	Completed	Treatment	BMI >30 kg/m2 / High Blood Pressure (Hypertension)	1
3	Completed	Treatment	Mania	1
3	Not Yet Recruiting	Treatment	Type1 Diabetes	1
3	Terminated	Treatment	Atrial Fibrillation (AF) / Heart Failure	1
4	Completed	Prevention	Kidney Stones	1
4	Completed	Treatment	Acute Myocardial Infarction (AMI) / Percutaneous Coronary Intervention	1
4	Completed	Treatment	BMI >30 kg/m2 / General Surgery / Hypoglycemia	1
4	Completed	Treatment	Coronary Artery Disease / High Blood Pressure (Hypertension)	1
4	Completed	Treatment	Diabetes / High Blood Pressure (Hypertension)	1
4	Completed	Treatment	Diabetes / High Blood Pressure (Hypertension) / Proteinuria	1
4	Completed	Treatment	Heart Disease, Ischemic	1
4	Completed	Treatment	High Blood Pressure (Hypertension)	2
4	Completed	Treatment	High Blood Pressure (Hypertension) / Metabolic Syndromes	1
4	Completed	Treatment	Marfan Syndrome	1
4	Completed	Treatment	Paroxysmal Supraventricular Tachycardia	1
4	Completed	Treatment	Rapid Ventricular Response Atrial Fibrillation	1
4	Recruiting	Diagnostic	Premature Ventricular Contraction (PVC)	1
4	Recruiting	Health Services Research	Cerebral Vasospasm	1
4	Terminated	Prevention	Keloid Scars	1
4	Unknown Status	Treatment	Cardiomyopathy / Heart Failure With Reduced Ejection Fraction (HFrEF) / Myocardial Diseases	1
4	Unknown Status	Treatment	Congestive Cardiomyopathy	1
4	Withdrawn	Treatment	Reversible cerebral vasoconstriction syndrome	1
Not Available	Active Not Recruiting	Treatment	Atrial Fibrillation (AF)	1
Not Available	Completed	Not Available	Coronary Heart Disease (CHD) / Verapamil Toxicity	1
Not Available	Completed	Not Available	Erectile Dysfunction	1
Not Available	Completed	Treatment	Arrhythmia / Atrial Fibrillation (AF)	1
Not Available	Completed	Treatment	Type 2 Diabetes Mellitus	1
Not Available	Not Yet Recruiting	Treatment	Tachycardia, Supraventricular	1
Not Available	Recruiting	Treatment	Ventricular premature beats	1
Not Available	Terminated	Treatment	Polyps, Nasal / Sinusitis	1
Not Available	Unknown Status	Treatment	Epilepsies / Seizures	1
Not Available	Withdrawn	Treatment	Catamenial Epilepsy	1

Pharmacoeconomics

Manufacturers

Mylan pharmaceuticals inc
Elan drug delivery inc
Gd searle llc
Fsc laboratories inc
Abraxis pharmaceutical products
Bedford laboratories div ben venue laboratories inc
Hospira inc
International medication system
Luitpold pharmaceuticals inc
Marsam pharmaceuticals llc
Smith and nephew solopak div smith and nephew
Solopak medical products inc
Ranbaxy laboratories inc
Glenmark generics ltd
Ivax pharmaceuticals inc sub teva pharmaceuticals usa
Par pharmaceutical inc
Pliva inc
Actavis elizabeth llc
Heritage pharmaceuticals inc
Mutual pharmaceutical co inc
Sandoz inc
Warner chilcott div warner lambert co
Watson laboratories inc

Packagers

Abbott Laboratories Ltd.
Advanced Pharmaceutical Services Inc.
Alza Corp.
Amerisource Health Services Corp.
Apotheca Inc.
A-S Medication Solutions LLC
Atlantic Biologicals Corporation
BASF Corp.
Cardinal Health
Caremark LLC
Comprehensive Consultant Services Inc.
Copley Chemical Co.
Dee Stevens and Son Feeder
Dept Health Central Pharmacy
Direct Dispensing Inc.
Dispensing Solutions
Diversified Healthcare Services Inc.
Duramed
Elan Pharmaceuticals Inc.
FSC Laboratories
GD Searle LLC
General Injectables and Vaccines Inc.
Glenmark Generics Ltd.
Golden State Medical Supply Inc.
Group Health Cooperative
H.J. Harkins Co. Inc.
Heartland Repack Services LLC
Hospira Inc.
Ivax Pharmaceuticals
Kaiser Foundation Hospital
Lake Erie Medical and Surgical Supply
Liberty Pharmaceuticals
Major Pharmaceuticals
Medisca Inc.
Murfreesboro Pharmaceutical Nursing Supply
Mylan
Nucare Pharmaceuticals Inc.
Palmetto Pharmaceuticals Inc.
PD-Rx Pharmaceuticals Inc.
Pfizer Inc.
Pharmaceutical Utilization Management Program VA Inc.
Pharmacia Inc.
Pharmedix
Physicians Total Care Inc.
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Prescript Pharmaceuticals
Ranbaxy Laboratories
Remedy Repack
Resource Optimization and Innovation LLC
Sandhills Packaging Inc.
Schwarz Pharma Inc.
Southwood Pharmaceuticals
Talbert Medical Management Corp.
Tya Pharmaceuticals
UDL Laboratories
United Research Laboratories Inc.
Vangard Labs Inc.
Watson Pharmaceuticals

Dosage forms

Form	Route	Strength
Tablet	Oral
Tablet, extended release	Oral	180 mg
Tablet, extended release	Oral	240 mg
Tablet, coated	Oral	120 mg/1
Tablet, coated	Oral	180 mg/1
Tablet, coated	Oral	240 mg/1
Tablet, extended release	Oral	120 mg
Tablet, extended release	Oral
Tablet, extended release	Oral
Tablet, film coated, extended release	Oral
Injection	Intravenous	5 mg/1mL
Capsule, delayed release pellets	Oral	120 mg/1
Capsule, delayed release pellets	Oral	180 mg/1
Capsule, extended release	Oral	100 mg/1
Capsule, extended release	Oral	120 mg/1
Capsule, extended release	Oral	180 mg/1
Capsule, extended release	Oral	200 mg/1
Capsule, extended release	Oral	240 mg/1
Capsule, extended release	Oral	300 mg/1
Injection	Intravenous	10 mg/4mL
Injection	Intravenous	2.5 mg/1mL
Injection	Intravenous	5 mg/2mL
Injection, solution	Intravenous	2.5 mg/1mL
Injection, solution	Intravenous	2.5 mg/1 mL
Powder	Not applicable	1 kg/1kg
Tablet	Oral	120 mg/1
Tablet	Oral	180 mg/1
Tablet	Oral	240 mg/1
Tablet	Oral	40 mg/1
Tablet	Oral	80 mg/1
Tablet, extended release	Oral	120 mg/1
Tablet, extended release	Oral	180 mg/1
Tablet, extended release	Oral	240 mg/301
Tablet, extended release	Oral	240 mg/1
Tablet, film coated	Oral	120 mg/1
Tablet, film coated	Oral	40 mg/1
Tablet, film coated	Oral	80 mg/1
Tablet, film coated, extended release	Oral	120 mg/1
Tablet, film coated, extended release	Oral	180 mg/1
Tablet, film coated, extended release	Oral	240 mg/1
Liquid	Intravenous
Solution	Intravenous
Capsule, delayed release pellets	Oral	240 mg/1
Capsule, delayed release pellets	Oral	360 mg/1
Capsule, extended release	Oral	120 mg
Capsule, extended release	Oral	180 mg
Capsule, extended release	Oral	240 mg

Prices

Unit description	Cost	Unit
Verelan 360 mg 24 Hour Capsule	6.82USD	capsule
Verelan 360 mg cap pellet	6.73USD	pellet
Verelan pm 300 mg cap pellet	5.87USD	pellet
Verelan 240 mg 24 Hour Capsule	4.76USD	capsule
Verelan 240 mg cap pellet	4.58USD	pellet
Verelan 180 mg 24 Hour Capsule	4.22USD	capsule
Verelan 180 mg cap pellet	4.06USD	pellet
Verelan pm 200 mg cap pellet	4.04USD	pellet
Verelan 120 mg cap pellet	3.87USD	pellet
Verapamil HCl CR 300 mg 24 Hour Capsule	3.82USD	capsule
Isoptin sr 240 mg tablet	3.32USD	tablet
Verapamil hcl powder	3.24USD	g
Calan SR 240 mg Controlled Release Tabs	3.15USD	tab
Isoptin SR 240 mg Controlled Release Tabs	3.14USD	tab
Verelan pm 100 mg cap pellet	3.13USD	pellet
Calan sr 240 mg caplet	3.09USD	caplet
Covera-HS 240 mg 24 Hour tablet	3.09USD	tablet
Covera-hs 240 mg tablet sa	2.97USD	tablet
Isoptin sr 180 mg tablet	2.9USD	tablet
Calan SR 180 mg Controlled Release Tabs	2.8USD	tab
Isoptin SR 180 mg Controlled Release Tabs	2.74USD	tab
Calan sr 180 mg caplet	2.7USD	caplet
Verapamil HCl CR 200 mg 24 Hour Capsule	2.62USD	capsule
Isoptin sr 120 mg tablet	2.29USD	tablet
Calan SR 120 mg Controlled Release Tabs	2.27USD	tab
Covera-HS 180 mg 24 Hour tablet	2.2USD	tablet
Isoptin SR 120 mg Controlled Release Tabs	2.16USD	tab
Calan sr 120 mg caplet	2.13USD	caplet
Covera-hs 180 mg tablet sa	2.11USD	tablet
Verapamil HCl CR 360 mg 24 Hour Capsule	2.1USD	capsule
Verapamil HCl CR 100 mg 24 Hour Capsule	2.04USD	capsule
Isoptin Sr 240 mg Sustained-Release Tablet	2.03USD	tablet
Calan sr 240 mg caplet sa	1.77USD	caplet
Verapamil HCl CR 240 mg 24 Hour Capsule	1.69USD	capsule
Verapamil HCl CR 240 mg Controlled Release Tabs	1.6USD	tab
Calan 120 mg tablet	1.56USD	tablet
Isoptin Sr 180 mg Sustained-Release Tablet	1.52USD	tablet
Verapamil HCl CR 180 mg 24 Hour Capsule	1.5USD	capsule
Calan sr 180 mg caplet sa	1.46USD	caplet
Verapamil HCl CR 120 mg 24 Hour Capsule	1.43USD	capsule
Verapamil HCl CR 180 mg Controlled Release Tabs	1.41USD	tab
Isoptin Sr 120 mg Sustained-Release Tablet	1.34USD	tablet
Calan 80 mg tablet	1.25USD	tablet
Verapamil 2.5 mg/ml vial	1.18USD	ml
Verapamil HCl CR 120 mg Controlled Release Tabs	1.12USD	tab
Apo-Verap Sr 240 mg Sustained-Release Tablet	0.91USD	tablet
Mylan-Verapamil Sr 240 mg Sustained-Release Tablet	0.91USD	tablet
Novo-Veramil Sr 240 mg Sustained-Release Tablet	0.91USD	tablet
Pms-Verapamil Sr 240 mg Sustained-Release Tablet	0.91USD	tablet
Calan 40 mg tablet	0.76USD	tablet
Apo-Verap Sr 120 mg Sustained-Release Tablet	0.72USD	tablet
Mylan-Verapamil Sr 120 mg Sustained-Release Tablet	0.72USD	tablet
Verapamil HCl 120 mg tablet	0.71USD	tablet
Apo-Verap Sr 180 mg Sustained-Release Tablet	0.69USD	tablet
Mylan-Verapamil Sr 180 mg Sustained-Release Tablet	0.69USD	tablet
Verapamil HCl 80 mg tablet	0.56USD	tablet
Apo-Verap 120 mg Tablet	0.45USD	tablet
Mylan-Verapamil 120 mg Tablet	0.45USD	tablet
Nu-Verap 120 mg Tablet	0.45USD	tablet
Verapamil 120 mg tablet	0.39USD	tablet
Verapamil 80 mg tablet	0.31USD	tablet
Verapamil HCl 40 mg tablet	0.29USD	tablet
Apo-Verap 80 mg Tablet	0.29USD	tablet
Mylan-Verapamil 80 mg Tablet	0.29USD	tablet
Nu-Verap 80 mg Tablet	0.29USD	tablet
Verapamil 40 mg tablet	0.28USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
Unlock Additional Data
US5785994	No	1998-07-28	2009-10-22
US6096339	No	2000-08-01	2017-04-04

Additional Data Available

Filed On

The date on which a patent was filed with the relevant government.

Learn more

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00394 mg/mL	ALOGPS
logP	5.23	ALOGPS
logP	5.04	ChemAxon
logS	-5.1	ALOGPS
pKa (Strongest Basic)	9.68	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	63.95 Å²	ChemAxon
Rotatable Bond Count	13	ChemAxon
Refractivity	132.65 m³·mol^-1	ChemAxon
Polarizability	51.7 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9371
Blood Brain Barrier	+	0.6323
Caco-2 permeable	+	0.738
P-glycoprotein substrate	Substrate	0.7874
P-glycoprotein inhibitor I	Inhibitor	0.9056
P-glycoprotein inhibitor II	Inhibitor	0.855
Renal organic cation transporter	Inhibitor	0.6259
CYP450 2C9 substrate	Non-substrate	0.8029
CYP450 2D6 substrate	Non-substrate	0.8706
CYP450 3A4 substrate	Substrate	0.7657
CYP450 1A2 substrate	Non-inhibitor	0.9553
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9026
CYP450 3A4 inhibitor	Inhibitor	0.796
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9181
Ames test	Non AMES toxic	0.8393
Carcinogenicity	Non-carcinogens	0.6463
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	3.4137 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.7687
hERG inhibition (predictor II)	Inhibitor	0.8188

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Mass Spectrum (Electron Ionization)	MS	splash10-0udi-3519000000-b5e0b9e0caac5cb57222
MS/MS Spectrum - Quattro_QQQ 10V, Positive	LC-MS/MS	splash10-004l-0702900000-6a46ea2d5eed6d8b01eb
MS/MS Spectrum - Quattro_QQQ 25V, Positive	LC-MS/MS	splash10-0006-4109800000-80d342090a0be3344e82
MS/MS Spectrum - Quattro_QQQ 40V, Positive	LC-MS/MS	splash10-054w-0954400000-2def387c7c93ab211423
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	LC-MS/MS	splash10-0a4i-0000900000-4cde9a4b3a4f83d16afc
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	LC-MS/MS	splash10-0a4i-0000900000-980b47834e505d54a0e6
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	LC-MS/MS	splash10-066r-0902800000-ae024239c46b33917426
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	LC-MS/MS	splash10-014i-0901000000-81d1159b3102cff76218
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	LC-MS/MS	splash10-014i-0900000000-d9c344fee7b45b4030e6
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	LC-MS/MS	splash10-0gb9-0914000000-070bdb975910e9aae99c
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	LC-MS/MS	splash10-03di-0390000000-f41d80462c5d06c4f001
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	LC-MS/MS	splash10-0097-2980000000-9a2ab0bcab33f7eaac6b
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	LC-MS/MS	splash10-0uxr-0900000000-252a9989a8511cb2db80
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	LC-MS/MS	splash10-0f79-0900000000-4fd6ca2c6c19c3bbf8f0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0a4i-0000900000-4365a47b2dc2f86bb272
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0a4i-0000900000-e6a2b357160bf5b92c22
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-066r-0902400000-d8eac2ccd0a767c7e432
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-014i-0901000000-688f3c2345c5d9ccb8a5
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-014i-0900000000-cd09f8a2be876936f662
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0uxr-0918000000-76641dd6dbc5cb05e79a
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0a4i-0000900000-05ea95eb1f39b6515212
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-066r-0902600000-a675e624692c25472ce8
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-014i-0901000000-70d820628d2613557239
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0gb9-0900000000-e3ca24cf75d574df08a8
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0uyi-0900000000-f3a9fa002c56d3e5689a
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0zg0-2900000000-101e077b890671063633
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0a4i-0000900000-84b4516ac84e6912cc15
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-066r-0902600000-bc1701c307e45ee4dcd7
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-014i-0901000000-6fbdab598bcb6147a4bf
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0gb9-0900000000-ce61116806eaa908681c
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0uxr-0900000000-ad3f25e02a7c8e66fb6a
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0zgr-2900000000-792b9009086561f6c398
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0uxr-0918000000-e7a5a3f8c88dc40683fd
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-0a4i-0000900000-4cde9a4b3a4f83d16afc
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-0a4i-0000900000-9a5c5240148f82cc6add
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-066r-0902800000-ae024239c46b33917426
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-014i-0901000000-81d1159b3102cff76218
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-014i-0900000000-2411d65dfe09741dde81
LC-MS/MS Spectrum - LC-ESI-IT , positive	LC-MS/MS	splash10-0gb9-0914000000-0463345a8ab0de7aa99e
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-014i-0900000000-42074ab645b7af0ef79f
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0zgi-0900000000-20360f78435d5f482709
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0uxr-0819000000-7f68ebd6e344adf12101
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-0uxr-0918000000-d3727bbe601b80eabfb3
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0a4i-0100900000-0a928f78000f291f031d
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-066r-0902600000-40f800e4a364d9ca214c
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0gb9-0900000000-4dea228d69d59705fc18
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0a4i-0500900000-c0bc440571b30d4b5b27
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-066r-0900300000-47a59c15bdbcbc62d6c6
1H NMR Spectrum	1D NMR	Not Applicable
[1H,13C] 2D NMR Spectrum	2D NMR	Not Applicable

Taxonomy

Description: This compound belongs to the class of organic compounds known as phenylbutylamines. These are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine.
Kingdom: Organic compounds
Super Class: Benzenoids
Class: Benzene and substituted derivatives
Sub Class: Phenylbutylamines
Direct Parent: Phenylbutylamines
Alternative Parents: Dimethoxybenzenes / Phenylpropanes / Phenethylamines / Phenoxy compounds / Anisoles / Aralkylamines / Alkyl aryl ethers / Trialkylamines / Nitriles / Organopnictogen compoundsHydrocarbon derivatives
show 1 more
Substituents: Phenylbutylamine / Dimethoxybenzene / O-dimethoxybenzene / Phenethylamine / Phenylpropane / Anisole / Phenol ether / Phenoxy compound / Methoxybenzene / Alkyl aryl ether
show 14 more
Molecular Framework: Aromatic homomonocyclic compounds
External Descriptors: tertiary amino compound, aromatic ether, nitrile, polyether (CHEBI:77733)

Targets

Details1. Voltage-dependent L-type calcium channel subunit alpha-1C

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1C
Uniprot ID: Q13936
Uniprot Name: Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight: 248974.1 Da

References

Dilmac N, Hilliard N, Hockerman GH: Molecular determinants of frequency dependence and Ca2+ potentiation of verapamil block in the pore region of Cav1.2. Mol Pharmacol. 2004 Nov;66(5):1236-47. Epub 2004 Jul 30. [PubMed:15286207]
Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T: The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits. Br J Pharmacol. 1998 Nov;125(5):1005-12. [PubMed:9846638]
Patel MK, Clunn GF, Lymn JS, Austin O, Hughes AD: Effect of serum withdrawal on the contribution of L-type calcium channels (CaV1.2) to intracellular Ca2+ responses and chemotaxis in cultured human vascular smooth muscle cells. Br J Pharmacol. 2005 Jul;145(6):811-7. [PubMed:15880143]
Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [PubMed:19125880]

Details2. Voltage-dependent N-type calcium channel subunit alpha-1B

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1B
Uniprot ID: Q00975
Uniprot Name: Voltage-dependent N-type calcium channel subunit alpha-1B
Molecular Weight: 262493.84 Da

References

Dobrev D, Milde AS, Andreas K, Ravens U: The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum. Br J Pharmacol. 1999 May;127(2):576-82. doi: 10.1038/sj.bjp.0702574. [PubMed:10385261]

Details3. Voltage-dependent P/Q-type calcium channel subunit alpha-1A

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1A
Uniprot ID: O00555
Uniprot Name: Voltage-dependent P/Q-type calcium channel subunit alpha-1A
Molecular Weight: 282362.39 Da

References

Dobrev D, Milde AS, Andreas K, Ravens U: The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum. Br J Pharmacol. 1999 May;127(2):576-82. doi: 10.1038/sj.bjp.0702574. [PubMed:10385261]

Details4. ATP-sensitive inward rectifier potassium channel 11

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Voltage-gated potassium channel activity
Specific Function: This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage ...
Gene Name: KCNJ11
Uniprot ID: Q14654
Uniprot Name: ATP-sensitive inward rectifier potassium channel 11
Molecular Weight: 43540.375 Da

References

Ninomiya T, Takano M, Haruna T, Kono Y, Horie M: Verapamil, a Ca2+ entry blocker, targets the pore-forming subunit of cardiac type KATP channel (Kir6.2). J Cardiovasc Pharmacol. 2003 Aug;42(2):161-8. doi: 10.1097/00005344-200308000-00002. [PubMed:12883317]

Details5. Voltage-dependent T-type calcium channel subunit alpha-1G

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Scaffold protein binding
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1G
Uniprot ID: O43497
Uniprot Name: Voltage-dependent T-type calcium channel subunit alpha-1G
Molecular Weight: 262468.62 Da

References

Freeze BS, McNulty MM, Hanck DA: State-dependent verapamil block of the cloned human Ca(v)3.1 T-type Ca(2+) channel. Mol Pharmacol. 2006 Aug;70(2):718-26. Epub 2006 May 12. [PubMed:16699084]
Bergson P, Lipkind G, Lee SP, Duban ME, Hanck DA: Verapamil block of T-type calcium channels. Mol Pharmacol. 2011 Mar;79(3):411-9. doi: 10.1124/mol.110.069492. Epub 2010 Dec 13. [PubMed:21149638]

Details6. Voltage-dependent T-type calcium channel subunit alpha-1H

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Scaffold protein binding
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1H
Uniprot ID: O95180
Uniprot Name: Voltage-dependent T-type calcium channel subunit alpha-1H
Molecular Weight: 259160.2 Da

References

Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [PubMed:18974361]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	141.25	N/A	N/A	21185626
IC 50 (nM)	145	N/A	N/A	15745831

Details7. Potassium voltage-gated channel subfamily H member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function: Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name: KCNH2
Uniprot ID: Q12809
Uniprot Name: Potassium voltage-gated channel subfamily H member 2
Molecular Weight: 126653.52 Da

References

Duan JJ, Ma JH, Zhang PH, Wang XP, Zou AR, Tu DN: Verapamil blocks HERG channel by the helix residue Y652 and F656 in the S6 transmembrane domain. Acta Pharmacol Sin. 2007 Jul;28(7):959-67. [PubMed:17588331]
Schneider J, Hauser R, Andreas JO, Linz K, Jahnel U: Differential effects of human ether-a-go-go-related gene (HERG) blocking agents on QT duration variability in conscious dogs. Eur J Pharmacol. 2005 Apr 4;512(1):53-60. [PubMed:15814090]
Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [PubMed:19125880]

Details8. Sodium-dependent serotonin transporter

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Unknown

General Function: Serotonin:sodium symporter activity
Specific Function: Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name: SLC6A4
Uniprot ID: P31645
Uniprot Name: Sodium-dependent serotonin transporter
Molecular Weight: 70324.165 Da

References

Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
Brown NL, Sirugue O, Worcel M: The effects of some slow channel blocking drugs on high affinity serotonin uptake by rat brain synaptosomes. Eur J Pharmacol. 1986 Apr 9;123(1):161-5. [PubMed:2940099]

Details9. Alpha-1A adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist
Curator comments: Inhibits receptor activity but shows little competition for binding. Likely an allosteric modulator.

General Function: Protein heterodimerization activity
Specific Function: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name: ADRA1A
Uniprot ID: P35348
Uniprot Name: Alpha-1A adrenergic receptor
Molecular Weight: 51486.005 Da

References

Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [PubMed:9570190]

Details10. Alpha-1B adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist
Curator comments: Inhibits receptor activity but shows little competition for binding. Likely an allosteric modulator.

General Function: Protein heterodimerization activity
Specific Function: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name: ADRA1B
Uniprot ID: P35368
Uniprot Name: Alpha-1B adrenergic receptor
Molecular Weight: 56835.375 Da

References

Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [PubMed:9570190]

Details11. Alpha-1D adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist
Curator comments: Inhibits receptor activity but shows little competition for binding. Likely an allosteric modulator.

General Function: Alpha1-adrenergic receptor activity
Specific Function: This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name: ADRA1D
Uniprot ID: P25100
Uniprot Name: Alpha-1D adrenergic receptor
Molecular Weight: 60462.205 Da

References

Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [PubMed:9570190]

Enzymes

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	1390	N/A	N/A	16248836
Ki (nM)	2970	N/A	N/A	16248836
Ki (nM)	5100	N/A	N/A	16248836
Ki (nM)	6460	N/A	N/A	16248836

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Wang YH, Jones DR, Hall SD: Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71. doi: 10.1124/dmd.104.001834. Epub 2005 Feb 2. [PubMed:15689501]
Flockhart Table of Drug Interactions [Link]
FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]

Details2. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Totah RA, Rettie AE: Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance. Clin Pharmacol Ther. 2005 May;77(5):341-52. doi: 10.1016/j.clpt.2004.12.267. [PubMed:15900280]
Busse D, Cosme J, Beaune P, Kroemer HK, Eichelbaum M: Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21. doi: 10.1007/bf00168924. [PubMed:8750925]
Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Details3. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Details4. Cytochrome P450 3A5

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Oxygen binding
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP3A5
Uniprot ID: P20815
Uniprot Name: Cytochrome P450 3A5
Molecular Weight: 57108.065 Da

References

Wang YH, Jones DR, Hall SD: Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71. doi: 10.1124/dmd.104.001834. Epub 2005 Feb 2. [PubMed:15689501]
Langaee TY, Gong Y, Yarandi HN, Katz DA, Cooper-DeHoff RM, Pepine CJ, Johnson JA: Association of CYP3A5 polymorphisms with hypertension and antihypertensive response to verapamil. Clin Pharmacol Ther. 2007 Mar;81(3):386-91. doi: 10.1038/sj.clpt.6100090. [PubMed:17339868]
Flockhart Table of Drug Interactions [Link]

Details5. Cytochrome P450 2C18

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C18
Uniprot ID: P33260
Uniprot Name: Cytochrome P450 2C18
Molecular Weight: 55710.075 Da

References

Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Details6. Cytochrome P450 2B6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Activator

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2B6
Uniprot ID: P20813
Uniprot Name: Cytochrome P450 2B6
Molecular Weight: 56277.81 Da

References

Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Details7. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name: CYP2C19
Uniprot ID: P33261
Uniprot Name: Cytochrome P450 2C19
Molecular Weight: 55930.545 Da

References

Busse D, Cosme J, Beaune P, Kroemer HK, Eichelbaum M: Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21. doi: 10.1007/bf00168924. [PubMed:8750925]
Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Details8. Cytochrome P450 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP1A2
Uniprot ID: P05177
Uniprot Name: Cytochrome P450 1A2
Molecular Weight: 58293.76 Da

References

Kroemer HK, Gautier JC, Beaune P, Henderson C, Wolf CR, Eichelbaum M: Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7. [PubMed:8232610]
Zhou SF, Yang LP, Zhou ZW, Liu YH, Chan E: Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009 Sep;11(3):481-94. doi: 10.1208/s12248-009-9127-y. Epub 2009 Jul 10. [PubMed:19590965]
Flockhart Table of Drug Interactions [Link]

Details9. Cytochrome P450 2E1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name: CYP2E1
Uniprot ID: P05181
Uniprot Name: Cytochrome P450 2E1
Molecular Weight: 56848.42 Da

References

Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Details10. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

FDA Approved Drug Products: Verelan® PM extended-release capsules [Link]

Details2. Alpha-1-acid glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Not Available
Specific Function: Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name: ORM1
Uniprot ID: P02763
Uniprot Name: Alpha-1-acid glycoprotein 1
Molecular Weight: 23511.38 Da

References

FDA Approved Drug Products: Verelan® PM extended-release capsules [Link]

Transporters

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	1041	N/A	N/A	17399990
EC 50 (nM)	120	N/A	N/A	9767638
EC 50 (nM)	20000	N/A	N/A	17064079 / 17936633 / 18257545 / 18524592
EC 50 (nM)	3100	N/A	N/A	11784143
IC 50 (nM)	134896288	N/A	N/A	17890094
IC 50 (nM)	14000	N/A	N/A	19402665
IC 50 (nM)	1480	N/A	N/A	12477351
IC 50 (nM)	2090	N/A	N/A	12477351
IC 50 (nM)	2100	N/A	N/A	10820137
IC 50 (nM)	2110	N/A	N/A	12477351
IC 50 (nM)	2210	N/A	N/A	12569305
IC 50 (nM)	2370	N/A	N/A	12477351
IC 50 (nM)	2440	N/A	N/A	12569305
IC 50 (nM)	2580	N/A	N/A	12569305
IC 50 (nM)	28900	N/A	N/A	11716514
IC 50 (nM)	3100	N/A	N/A	10386932
IC 50 (nM)	38200	N/A	N/A	11716514
IC 50 (nM)	400	N/A	N/A	12699389 / 15240100
IC 50 (nM)	4200	N/A	N/A	11454724 / 11716514
IC 50 (nM)	42000	N/A	N/A	11716514
IC 50 (nM)	446500	N/A	N/A	11716514
IC 50 (nM)	4571	N/A	N/A	17890094 / 18083034
IC 50 (nM)	4700	N/A	N/A	11716514
IC 50 (nM)	4780	N/A	N/A	12569305
IC 50 (nM)	500	N/A	N/A	22112208
IC 50 (nM)	53000	N/A	N/A	10386932
IC 50 (nM)	5330	N/A	N/A	12569305
IC 50 (nM)	5520	N/A	N/A	12569305
IC 50 (nM)	5754	N/A	N/A	18083034
IC 50 (nM)	5800	N/A	N/A	18083034
IC 50 (nM)	6300	N/A	N/A	12699389
IC 50 (nM)	6500	N/A	N/A	11716514
IC 50 (nM)	6607	N/A	N/A	17890094 / 18083034
IC 50 (nM)	8440	N/A	N/A	15359574
IC 50 (nM)	9800	N/A	N/A	21354800
Ki (nM)	15100	N/A	N/A	12134945
Ki (nM)	1600	N/A	N/A	12477351
Ki (nM)	2500	N/A	N/A	12477351
Ki (nM)	300	N/A	N/A	12477351

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [PubMed:19125880]
FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	6800	N/A	N/A	18788725

Details2. Solute carrier family 22 member 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Secondary active organic cation transmembrane transporter activity
Specific Function: Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name: SLC22A1
Uniprot ID: O15245
Uniprot Name: Solute carrier family 22 member 1
Molecular Weight: 61153.345 Da

References

Cho SK, Kim CO, Park ES, Chung JY: Verapamil decreases the glucose-lowering effect of metformin in healthy volunteers. Br J Clin Pharmacol. 2014 Dec;78(6):1426-32. doi: 10.1111/bcp.12476. [PubMed:25060604]
Boxberger KH, Hagenbuch B, Lampe JN: Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated neurotransmitter uptake. Drug Metab Dispos. 2014 Jun;42(6):990-5. doi: 10.1124/dmd.113.055095. Epub 2014 Mar 31. [PubMed:24688079]

Details3. Solute carrier family 22 member 4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Symporter activity
Specific Function: Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name: SLC22A4
Uniprot ID: Q9H015
Uniprot Name: Solute carrier family 22 member 4
Molecular Weight: 62154.48 Da

References

Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [PubMed:10215651]

Details4. Solute carrier family 22 member 5

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Symporter activity
Specific Function: Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name: SLC22A5
Uniprot ID: O76082
Uniprot Name: Solute carrier family 22 member 5
Molecular Weight: 62751.08 Da

References

Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [PubMed:10525100]
Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. [PubMed:11160873]

Details5. Canalicular multispecific organic anion transporter 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Organic anion transmembrane transporter activity
Specific Function: May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name: ABCC3
Uniprot ID: O15438
Uniprot Name: Canalicular multispecific organic anion transporter 2
Molecular Weight: 169341.14 Da

References

Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [PubMed:11585759]

Details6. Solute carrier organic anion transporter family member 1B1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name: SLCO1B1
Uniprot ID: Q9Y6L6
Uniprot Name: Solute carrier organic anion transporter family member 1B1
Molecular Weight: 76447.99 Da

References

Oostendorp RL, van de Steeg E, van der Kruijssen CM, Beijnen JH, Kenworthy KE, Schinkel AH, Schellens JH: Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors. Drug Metab Dispos. 2009 Apr;37(4):917-23. doi: 10.1124/dmd.108.024901. Epub 2009 Jan 12. [PubMed:19139163]

Details7. Solute carrier organic anion transporter family member 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name: SLCO1A2
Uniprot ID: P46721
Uniprot Name: Solute carrier organic anion transporter family member 1A2
Molecular Weight: 74144.105 Da

References

Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [PubMed:10421612]

Details8. Multidrug resistance-associated protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Transporter activity
Specific Function: Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name: ABCC1
Uniprot ID: P33527
Uniprot Name: Multidrug resistance-associated protein 1
Molecular Weight: 171589.5 Da

References

Perrotton T, Trompier D, Chang XB, Di Pietro A, Baubichon-Cortay H: (R)- and (S)-verapamil differentially modulate the multidrug-resistant protein MRP1. J Biol Chem. 2007 Oct 26;282(43):31542-8. doi: 10.1074/jbc.M703964200. Epub 2007 Jul 22. [PubMed:17646169]

Details9. Multidrug resistance-associated protein 4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Atpase activity, coupled to transmembrane movement of substances
Specific Function: May be an organic anion pump relevant to cellular detoxification.
Gene Name: ABCC4
Uniprot ID: O15439
Uniprot Name: Multidrug resistance-associated protein 4
Molecular Weight: 149525.33 Da

References

Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. [PubMed:12036927]
Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. [PubMed:14643890]

Details10. Multidrug resistance-associated protein 7

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Atpase activity, coupled to transmembrane movement of substances
Specific Function: ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name: ABCC10
Uniprot ID: Q5T3U5
Uniprot Name: Multidrug resistance-associated protein 7
Molecular Weight: 161627.375 Da

References

Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [PubMed:12527806]

Details11. Multidrug and toxin extrusion protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Monovalent cation:proton antiporter activity
Specific Function: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name: SLC47A1
Uniprot ID: Q96FL8
Uniprot Name: Multidrug and toxin extrusion protein 1
Molecular Weight: 61921.585 Da

References

Radchenko M, Symersky J, Nie R, Lu M: Structural basis for the blockade of MATE multidrug efflux pumps. Nat Commun. 2015 Aug 6;6:7995. doi: 10.1038/ncomms8995. [PubMed:26246409]

Details12. Multidrug and toxin extrusion protein 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Drug transmembrane transporter activity
Specific Function: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name: SLC47A2
Uniprot ID: Q86VL8
Uniprot Name: Multidrug and toxin extrusion protein 2
Molecular Weight: 65083.915 Da

References

Radchenko M, Symersky J, Nie R, Lu M: Structural basis for the blockade of MATE multidrug efflux pumps. Nat Commun. 2015 Aug 6;6:7995. doi: 10.1038/ncomms8995. [PubMed:26246409]

Drug created on June 13, 2005 07:24 / Updated on January 23, 2020 17:13

Verapamil

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Structure for Verapamil (DB00661)

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Enzymes

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