Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C27H38N2O4.ClH |
| Molecular Weight | 491.063 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1
InChI
InChIKey=DOQPXTMNIUCOSY-UHFFFAOYSA-N
InChI=1S/C27H38N2O4.ClH/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;1H
DescriptionCurator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00661
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00661
Verapamil is a FDA approved drug used to treat high blood pressure and to control chest pain. Verapamil is an L-type calcium channel blocker that also has antiarrythmic activity. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias. Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known.
CNS Activity
Curator's Comment: As a lipophilic substance, verapamil easily crosses
the blood–brain barrier. Verapamil is, however, a
substrate for the efflux transporter P-glycoprotein
(P-gp) in the blood–brain barrier. The P-pg restricts
net brain uptake of verapamil by immediately transporting
it out of the brain.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 3.4 µM [IC50] | |||
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | CALAN Approved UseCALAN 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 Date1981 |
|||
| Primary | CALAN Approved UseCALAN 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 Date1981 |
|||
| Primary | CALAN Approved UseCALAN 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 Date1981 |
Cmax
| 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 |
T1/2
| 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 |
Funbound
| 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 |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 146.0 |
likely | |||
| moderate [IC50 23 uM] | ||||
Page: 99.0 |
weak | |||
| yes [IC50 1.23 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | yes (co-administration study) Comment: Co-administration of multiple doses of 10 mg of verapamil with 80 mg simvastatin resulted in exposure to simvastatin 2.5-fold that following simvastatin alone; Clinically significant interactions have been reported with inhibitors of CYP3A4 (e.g., erythromycin, ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (e.g., rifampin) have caused a lowering of plasma levels of verapamil Page: 7.0 |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| [Demonstration of a major preexcitation syndrome during treatment of auricular flutter using intravenous injection of verapamil]. | 1975 |
|
| [Mapping electrocardiographic fields in heart hypertrophy]. | 1998 |
|
| [The importance of the ion-transport systems of the sarcolemma and sarcoplasmic reticulum in changing rat cardiac contractile function under a hypersodium medium]. | 1999 Apr |
|
| Successful resuscitation of a verapamil-intoxicated patient with percutaneous cardiopulmonary bypass. | 1999 Dec |
|
| Increase in doxorubicin cytotoxicity by carvedilol inhibition of P-glycoprotein activity. | 1999 Dec 1 |
|
| Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice. | 1999 Feb |
|
| P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. | 1999 Oct |
|
| Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites. | 2000 Apr |
|
| 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 |
|
| Effect of metoprolol and verapamil administered separately and concurrently after single doses on liver blood flow and drug disposition. | 2000 May |
|
| Transition-state formation in ATPase-negative mutants of human MDR1 protein. | 2000 Oct 5 |
|
| Monitoring of cellular resistance to cancer chemotherapy: drug retention and efflux. | 2001 |
|
| Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment. | 2001 Feb |
|
| [Treatment of cluster headache]. | 2001 Feb |
|
| Pharmacologic management of atrial fibrillation: current therapeutic strategies. | 2001 Feb |
|
| Dysfunction of polymorphonuclear leukocytes in uremia: role of parathyroid hormone. | 2001 Feb |
|
| Intra- and intercellular Ca(2+)-transient propagation in normal and high glucose solutions in ROS cells during mechanical stimulation. | 2001 Feb |
|
| Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells. | 2001 Feb |
|
| A flow cell assay for evaluation of whole cell drug efflux kinetics: analysis of paclitaxel efflux in CCRF-CEM leukemia cells overexpressing P-glycoprotein. | 2001 Feb |
|
| Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery. | 2001 Feb 2 |
|
| Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats. | 2001 Feb 2 |
|
| Cardiovascular action of a cardioselective Ca(2+)channel blocker AH-1058 in conscious dogs assessed by telemetry. | 2001 Feb 9 |
|
| Ionized magnesium in the homeostasis of cells: intracellular threshold for Mg(2+) in human platelets. | 2001 Jan |
|
| A novel zidovudine uptake system in microglia. | 2001 Jan |
|
| Evaluation of a vincristine resistant Caco-2 cell line for use in a calcein AM extrusion screening assay for P-glycoprotein interaction. | 2001 Jan |
|
| Left ventricular midwall function improves with antihypertensive therapy and regression of left ventricular hypertrophy in patients with asymptomatic hypertension. | 2001 Jan 1 |
|
| Behavioural and anti-psychotic effects of Ca2+ channel blockers in rhesus monkey. | 2001 Jan 26 |
|
| Improved intestinal absorption of sulpiride in rats with synchronized oral delivery systems. | 2001 Jan 29 |
|
| The effects of LY393613, nimodipine and verapamil, in focal cerebral ischaemia. | 2001 Jan 5 |
Sample Use Guides
Angina: Clinical trials show that the usual dose is 80 mg to 120 mg three times a day.
However, 40 mg three times a day may be warranted in patients who may have an
increased response to verapamil (eg, decreased hepatic function, elderly, etc). Upward
titration should be based on therapeutic efficacy and safety evaluated approximately eight
hours after dosing. Dosage may be increased at daily (eg, patients with unstable angina)
or weekly intervals until optimum clinical response is obtained.
Arrhythmias: The dosage in digitalized patients with chronic atrial fibrillation (see
PRECAUTIONS) ranges from 240 to 320 mg/day in divided (t.i.d. or q.i.d.) doses. The
dosage for prophylaxis of PSVT (non-digitalized patients) ranges from 240 to
480 mg/day in divided (t.i.d. or q.i.d.) doses. In general, maximum effects for any given
dosage will be apparent during the first 48 hours of therapy.
Essential hypertension: Dose should be individualized by titration. The usual initial
monotherapy dose in clinical trials was 80 mg three times a day (240 mg/day). Daily
dosages of 360 and 480 mg have been used but there is no evidence that dosages beyond
360 mg provided added effect. Consideration should be given to beginning titration at
40 mg three times per day in patients who might respond to lower doses, such as the
elderly or people of small stature. The antihypertensive effects of CALAN are evident
within the first week of therapy. Upward titration should be based on therapeutic
efficacy, assessed at the end of the dosing interval.
Route of Administration:
Other
| Name | Type | Language | ||
|---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Brand Name | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
NCI_THESAURUS |
C333
Created by
admin on Fri Dec 15 15:00:34 GMT 2023 , Edited by admin on Fri Dec 15 15:00:34 GMT 2023
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
62969
Created by
admin on Fri Dec 15 15:00:34 GMT 2023 , Edited by admin on Fri Dec 15 15:00:34 GMT 2023
|
PRIMARY | |||
|
100000090474
Created by
admin on Fri Dec 15 15:00:34 GMT 2023 , Edited by admin on Fri Dec 15 15:00:34 GMT 2023
|
PRIMARY | |||
|
C2827
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
152-11-4
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
V3888OEY5R
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
152-11-4
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
205-800-5
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
657799
Created by
admin on Fri Dec 15 15:00:34 GMT 2023 , Edited by admin on Fri Dec 15 15:00:34 GMT 2023
|
PRIMARY | |||
|
1711202
Created by
admin on Fri Dec 15 15:00:34 GMT 2023 , Edited by admin on Fri Dec 15 15:00:34 GMT 2023
|
PRIMARY | |||
|
m11414
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | Merck Index | ||
|
SUB05088MIG
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
DTXSID2034095
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
CHEMBL6966
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
VERAPAMIL HYDROCHLORIDE
Created by
admin on Fri Dec 15 15:00:34 GMT 2023 , Edited by admin on Fri Dec 15 15:00:34 GMT 2023
|
PRIMARY | Description: A white or almost white, crystalline powder; odourless or almost odourless. Solubility: Soluble in 20 parts of water; sparingly soluble in ethanol (~750 g/l) TS. Category: Antianginal drug. Storage: Verapamil hydrochloride should be kept in a well-closed container, protected from light. Definition: Verapamil hydrochloride contains not less than 99.0% and not more than 101.0% of C27H38N2O4,HCl, calculated with reference to the dried substance. | ||
|
DBSALT000534
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
V3888OEY5R
Created by
admin on Fri Dec 15 15:00:33 GMT 2023 , Edited by admin on Fri Dec 15 15:00:33 GMT 2023
|
PRIMARY | |||
|
203138
Created by
admin on Fri Dec 15 15:00:34 GMT 2023 , Edited by admin on Fri Dec 15 15:00:34 GMT 2023
|
PRIMARY | RxNorm | ||
|
272366
Created by
admin on Fri Dec 15 15:00:34 GMT 2023 , Edited by admin on Fri Dec 15 15:00:34 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
SUBSTANCE RECORD
