U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H26N2O4S
Molecular Weight 414.5198
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DILTIAZEM

SMILES

CC(=O)O[C@]1([H])[C@]([H])(c2ccc(cc2)OC)Sc3ccccc3N(CCN(C)C)C1=O

InChI

InChIKey=HSUGRBWQSSZJOP-RTWAWAEBSA-N
InChI=1S/C22H26N2O4S/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3/h5-12,20-21H,13-14H2,1-4H3/t20-,21+/m1/s1

HIDE SMILES / InChI

Molecular Formula C22H26N2O4S
Molecular Weight 414.5198
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Diltiazem is a nondihydropyridines calcium channel blocker used in the treatment of hypertension, angina pectoris, and some types of arrhythmia. Diltiazem produces its antihypertensive effect primarily by relaxation of vascular smooth muscle and the resultant decrease in peripheral vascular resistance.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CARDIZEM

Approved Use

Diltiazem produces its antihypertensive effect primarily by relaxation of vascular smooth muscle and the resultant decrease in peripheral vascular resistance. The magnitude of blood pressure reduction is related to the degree of hypertension; thus hypertensive individuals experience an antihypertensive effect, whereas there is only a modest fall in blood pressure in normotensives.

Launch Date

405302400000
Primary
CARDIZEM

Approved Use

Diltiazem has been shown to produce increases in exercise tolerance, probably due to its ability to reduce myocardial oxygen demand. This is accomplished via reductions in heart rate and systemic blood pressure at submaximal and maximal work loads. Diltiazem has been shown to be a potent dilator of coronary arteries, both epicardial and subendocardial. Spontaneous and ergonovine-induced coronary artery spasm are inhibited by diltiazem.

Launch Date

405302400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
166.4 ng/mL
240 mg 1 times / day steady-state, oral
dose: 240 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DILTIAZEM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2410 ng × h/mL
240 mg 1 times / day steady-state, oral
dose: 240 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DILTIAZEM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.5 h
360 mg single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DILTIAZEM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
25%
360 mg single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DILTIAZEM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
weak
yes [IC50 0.6 uM]
yes [IC50 11 uM]
yes [IC50 120 uM]
yes (co-administration study)
Comment: Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins.
yes [Ki 117 uM]
yes [Ki 12.5 uM]
yes [Ki 77.7 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
no
no (pharmacogenomic study)
Comment: results suggest that CYP3A5*3 has only a minor effect on the pharmacokinetics and metabolism of diltiazem
yes
yes
yes
weak (pharmacogenomic study)
Comment: Two of the most frequent alleles, CYP3A5 3 and CYP2D6 10, among Chinese do not have major impacts on the disposition of diltiazem and N-desmethyl diltiazem. However, the desacetyl diltiazem showed 2-fold accumulation in individuals with CYP2D6 10/10 genotype
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect.
2000 Jan
Physiology in medicine: importance of hypoxic pulmonary vasoconstriction in maintaining arterial oxygenation during acute respiratory failure.
2001
Calcium channel blockers for neuroleptic-induced tardive dyskinesia.
2001
[Unexpected formation of spiro(benzofuran-2,2'-(1,4)benzothiazines) from aurones].
2001 Apr
Atrial fibrillation: is rate stabilization a valid clinical strategy?
2001 Apr
Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease.
2001 Apr
Ionic mechanisms of aglycemic axon injury in mammalian central white matter.
2001 Apr
Effect of the calcium channel blockers nifedipine and diltiazem on pentylenetetrazole kindling-provoked amnesia in rats.
2001 Apr
Slowing the progression of renal disease in diabetic patients.
2001 Apr
Topical diltiazem ointment in the treatment of chronic anal fissure.
2001 Apr
An extremely severe case of cutaneous calcinosis with juvenile dermatomyositis, and successful treatment with diltiazem.
2001 Apr
Pharmacokinetics of cyclosporine in heart transplant recipients receiving metabolic inhibitors.
2001 Apr
Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs.
2001 Apr
Voltage-dependent calcium channels in the rat retina: involvement in NMDA-stimulated influx of calcium.
2001 Apr
Drug release from and mechanical properties of press-coated tablets with hydroxypropylmethylcellulose acetate succinate and plasticizers in the outer shell.
2001 Apr 17
Involvement of calcium signaling in the fibronectin-stimulated macrophage recognition of oxidatively damaged erythrocytes.
2001 Apr 23
Atrial fibrillation control and cardioversion.
2001 Apr 7
A case of lichenoid purpura possibly caused by diltiazem hydrochloride.
2001 Feb
Susac's syndrome: beneficial effects of corticosteroid therapy in a Japanese case.
2001 Feb
The protective effects of high dose ascorbic acid and diltiazem on myocardial ischaemia-reperfusion injury.
2001 Feb
Pharmacological interventions of cyanide-induced cytotoxicity and DNA damage in isolated rat thymocytes and their protective efficacy in vivo.
2001 Feb 3
Diltiazem for nocturnal leg cramps.
2001 Jan
Design and evaluation of microcapsules of diltiazem hydrochloride.
2001 Jan-Feb
Verapamil versus amlodipine in proteinuric non-diabetic nephropathies treated with trandolapril (VVANNTT study): design of a prospective randomized multicenter trial.
2001 Jan-Feb
Protein kinase C activates store-operated Ca(2+) channels in human glomerular mesangial cells.
2001 Jul 13
Na+ effects on mitochondrial respiration and oxidative phosphorylation in diabetic hearts.
2001 Jun
Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias.
2001 Jun
Electrophysiological characteristics of rat gustatory cyclic nucleotide--gated channel expressed in Xenopus oocytes.
2001 Jun
Photostability and phototoxicity studies on diltiazem.
2001 Jun
Analysis of multicomponent formulations containing phenylpropanolamine hydrochloride, caffeine and diazepam by using LC.
2001 Jun
Adsorptive stripping voltammetric determination of antihypertensive agent: diltiazem.
2001 Jun
cAMP modulates the excitability of immortalized H=hypothalamic (GT1) neurons via a cyclic nucleotide gated channel.
2001 Jun
Smooth muscle relaxation and local hydraulic impedance properties of the aorta.
2001 Jun
Calcium signaling pathways utilized by P2X receptors in freshly isolated preglomerular MVSMC.
2001 Jun
Contraction of human colonic circular smooth muscle cells is inhibited by the calcium channel blocker pinaverium bromide.
2001 Jun
An alternative method to the evaluation of similarity factor in dissolution testing.
2001 Jun 4
Clinical outcomes of aneurysmal subarachnoid hemorrhage patients treated with oral diltiazem and limited intensive care management.
2001 Mar
Effect of simvastatin on vascular smooth muscle responsiveness: involvement of Ca(2+) homeostasis.
2001 Mar
Effect of magnesium stearate or calcium stearate as additives on dissolution profiles of diltiazem hydrochloride from press-coated tablets with hydroxypropylmethylcellulose acetate succinate in the outer shell.
2001 Mar 23
Heart rate-lowering calcium antagonists in hypertensive post-myocardial infarction patients.
2001 May
Inhibitory effects of TA-993 and its metabolite MB3 on platelet activation induced by collagen and U-46619 in human platelets.
2001 May
Dilitiazem reduces nitric oxide production by human immune cells.
2001 May
Ca2+-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells.
2001 May
Left ventricular diastolic heart failure with normal left ventricular systolic function in older persons.
2001 May
Calcium-dependent effects of melatonin inhibition of glutamatergic response in rat striatum.
2001 May
The effects of diltiazem on hemodynamics and seizure duration during electroconvulsive therapy.
2001 May
Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: transmembrane exchange and cytoplasmic binding process.
2001 May
Nifedipine-activated Ca(2+) permeability in newborn rat cortical collecting duct cells in primary culture.
2001 May
[Attempted suicide with sustained release diltiazem].
2001 May 12
Characterization of drug release from diltiazem-loaded polylactide microspheres prepared using sodium caseinate and whey protein as emulsifying agents.
2001 May-Jun
Patents

Sample Use Guides

In Vivo Use Guide
When used as monotherapy, reasonable starting doses are 180 to 240 mg once daily, although some patients may respond to lower doses. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, dosage adjustments should be scheduled accordingly. The usual dosage range studied in clinical trials was 240 to 360 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. Dosages for the treatment of angina should be adjusted to each patient's needs, starting with a dose of 120 or 180 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. When necessary, titration may be carried out over a 7- to 14-day period.
Route of Administration: Oral
In Vitro Use Guide
Tissue homogenate of cerebral cortext and heart containing calcium channel receptors was used in a radioligand-binding assays. Cerebral cortices of male SD rats were homogenized. Hearts were also removed, perfused through aorta with ice-cold saline solution, and homogenized. Subsequently, the cardiac homogenates were filtered through four layers of cloth. Both cortical and cardiac homogenates were washed 5 times by centrifugation for 10 min at 48000 g. The final pelle was resuspended to a conc. of 50 mg of original wet tissue wt/mL of buffer and stored at -70°C. Tissue homogenate (200 uL) was incubated for 90 min in a dark room at 0°C with 100 uL of [3H]nitreddipine (3x10^-10M, 87 Ci/mmol) and 100 uL of the test compound dissolved in DMSO in 50 mM of Na-Hepes buffer, pH 7.4. The incubations were stopped by adding 4 mL of cold buffer followed by rapid filtratoin through glass fiber filter disks. The samples were subsequently washed 3 times with 4.5 mL of the same buffer and placed into scintill. vials. Diltiazem inhibited binding of [3H]nitrendipine with Ki of 21 nM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 11:38:34 UTC 2021
Edited
by admin
on Sat Jun 26 11:38:34 UTC 2021
Record UNII
EE92BBP03H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DILTIAZEM
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
DILTIAZEM [HSDB]
Common Name English
DILTIAZEM EXTENDED RELEASE
Common Name English
DILTIAZEM [VANDF]
Common Name English
DILTIAZEM [MI]
Common Name English
SURAZEM
Brand Name English
1,5-BENZOTHIAZEPIN-4(5H)-ONE, 3-(ACETYLOXY)-5-(U2-(DIMETHYLAMINO)ETHYL)-2,3-DIHYDRO-2-(4-METHOXYPHENYL)-, (+)-CIS-
Common Name English
DILTIAZEM [INN]
Common Name English
(+)-5-(2-(DIMETHYLAMINO)ETHYL)-CIS-2,3-DIHYDRO-3-HYDROXY-2-(P-METHOXYPHENYL)-1,5-BENZOTHIAZEPIN-4(5H)-ONE ACETATE (ESTER)
Common Name English
DILTIAZEM [WHO-DD]
Common Name English
DITIAZ [VANDF]
Common Name English
Classification Tree Code System Code
WHO-VATC QC08DB01
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
WHO-ATC C08DB01
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
NDF-RT N0000000069
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
LIVERTOX 311
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
WHO-ATC C05AE03
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
NDF-RT N0000175566
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
NCI_THESAURUS C333
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
Code System Code Type Description
FDA UNII
EE92BBP03H
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
CAS
42399-41-7
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
IUPHAR
2298
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
PUBCHEM
39186
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
ECHA (EC/EINECS)
255-796-4
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
ChEMBL
CHEMBL23
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
DRUG BANK
DB00343
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
HSDB
6528
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
INN
3433
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
MERCK INDEX
M4494
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY Merck Index
EVMPD
SUB07148MIG
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
LACTMED
Diltiazem
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
EPA CompTox
42399-41-7
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
MESH
D004110
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
DRUG CENTRAL
897
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
RXCUI
3443
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
DILTIAZEM
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
NCI_THESAURUS
C61725
Created by admin on Sat Jun 26 11:38:35 UTC 2021 , Edited by admin on Sat Jun 26 11:38:35 UTC 2021
PRIMARY
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