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

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H26N2O4S
Molecular Weight 414.518
Optical Activity ( + )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DILTIAZEM

SMILES

COC1=CC=C(C=C1)[C@@H]2SC3=CC=CC=C3N(CCN(C)C)C(=O)[C@@H]2OC(C)=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 414.518
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

Primary TargetPharmacologyConditionPotency
21.0 nM [Ki]
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

1982
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

1982
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
Calcium-channel blocker withdrawal in a pregnant woman.
1999 Jan
Statins and peripheral neuropathy.
1999 Jan
Rapid reversal of life-threatening diltiazem-induced tetany with calcium chloride.
1999 Nov
Antihypertensive efficacy and tolerability of once-daily sustained-release diltiazem alone and in combination with ramipril in hypertension.
1999 Oct
Diltiazem causes open channel block of recombinant 5-HT3 receptors.
1999 Sep 15
Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect.
2000 Jan
Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects.
2000 Oct
Nitroglycerin is preferable to diltiazem for prevention of coronary bypass conduit spasm.
2000 Sep
Calcium channel blockers for neuroleptic-induced tardive dyskinesia.
2001
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
Pharmacokinetics of cyclosporine in heart transplant recipients receiving metabolic inhibitors.
2001 Apr
Susac's syndrome: beneficial effects of corticosteroid therapy in a Japanese case.
2001 Feb
Endothelin-1 enhances eicosanoids-induced coronary smooth muscle contraction by activating specific protein kinase C isoforms.
2001 Feb
Mechanical stress stimulates phospholipase C activity and intracellular calcium ion levels in neonatal rat cardiomyocytes.
2001 Feb
L-type calcium channel blockers and EGTA enhance superoxide production in cardiac fibroblasts.
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 downregulates IL-12 production by human dendritic cells.
2001 Feb-Mar
Diltiazem affects human dendritic cell maturation.
2001 Feb-Mar
Diltiazem for nocturnal leg cramps.
2001 Jan
Heart rate-lowering and -regulating effects of once-daily sustained-release diltiazem.
2001 Jan
Pharmacokinetic interaction between single oral doses of diltiazem and sirolimus in healthy volunteers.
2001 Jan
Prehospital management of rapid atrial fibrillation: recommendations for treatment protocols.
2001 Jan
Photostability and phototoxicity studies on diltiazem.
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
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
Positive and negative contractile effects of somatostatin-14 on rat ventricular cardiomyocytes.
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
Inhibition by nifedipine of adherence- and activated macrophage-induced death of human gingival fibroblasts.
2001 Mar 9
Randomized trial of rhythm or rate control in atrial fibrillation: the Pharmacological Intervention in Atrial Fibrillation Trial (PIAF).
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
Characterization of drug release from diltiazem-loaded polylactide microspheres prepared using sodium caseinate and whey protein as emulsifying agents.
2001 May-Jun
Study of processing parameters influencing the properties of diltiazem hydrochloride microspheres.
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 Dec 16 16:27:04 GMT 2023
Edited
by admin
on Sat Dec 16 16:27:04 GMT 2023
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 [WHO-DD]
Common 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
DITIAZ [VANDF]
Common Name English
Classification Tree Code System Code
WHO-VATC QC08DB01
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
WHO-ATC C08DB01
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
NDF-RT N0000000069
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
LIVERTOX NBK547898
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
WHO-ATC C05AE03
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
NDF-RT N0000175566
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
NCI_THESAURUS C333
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
Code System Code Type Description
FDA UNII
EE92BBP03H
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
CAS
42399-41-7
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
IUPHAR
2298
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
PUBCHEM
39186
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
ECHA (EC/EINECS)
255-796-4
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
DAILYMED
EE92BBP03H
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
ChEMBL
CHEMBL23
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
DRUG BANK
DB00343
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
HSDB
6528
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
INN
3433
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
MERCK INDEX
m4494
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY Merck Index
EVMPD
SUB07148MIG
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
LACTMED
Diltiazem
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
EPA CompTox
DTXSID9022940
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
MESH
D004110
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
DRUG CENTRAL
897
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
CHEBI
101278
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
RXCUI
3443
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY RxNorm
WIKIPEDIA
DILTIAZEM
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
NCI_THESAURUS
C61725
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
SMS_ID
100000082630
Created by admin on Sat Dec 16 16:27:05 GMT 2023 , Edited by admin on Sat Dec 16 16:27:05 GMT 2023
PRIMARY
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