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
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
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095229 |
21.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | CARDIZEM Approved UseDiltiazem 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 Date1982 |
|||
Primary | CARDIZEM Approved UseDiltiazem 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 Date1982 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
166.4 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11329099 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2410 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11329099 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical 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
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
no | no (pharmacogenomic study) Comment: results suggest that CYP3A5*3 has only a minor effect on the pharmacokinetics and metabolism of diltiazem Sources: https://pubmed.ncbi.nlm.nih.gov/16024008/ |
|||
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
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
[Sinoatrial block induced by therapeutic doses of diltiazem. Report of 3 cases]. | 2000 Dec |
|
Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect. | 2000 Jan |
|
Calcium channel blockers for neuroleptic-induced tardive dyskinesia. | 2001 |
|
[Dilren efficacy in postmyocardial infarction patients]. | 2001 |
|
Differential effects of enalapril and irbesartan in experimental papillary necrosis. | 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 |
|
Topical diltiazem ointment in the treatment of chronic anal fissure. | 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 |
|
Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats. | 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 |
|
The protective effects of high dose ascorbic acid and diltiazem on myocardial ischaemia-reperfusion injury. | 2001 Feb |
|
Endothelin-1 enhances eicosanoids-induced coronary smooth muscle contraction by activating specific protein kinase C isoforms. | 2001 Feb |
|
Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia. | 2001 Feb |
|
Calcium channel blocker D-cis-diltiazem does not slow retinal degeneration in the PDE6B mutant rcd1 canine model of retinitis pigmentosa. | 2001 Feb 25 |
|
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 |
|
Muscarinic activation of transient inward current and contraction in canine colon circular smooth muscle cells. | 2001 Jan |
|
An in vitro investigation of the suitability of press-coated tablets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydrophobic additives in the outer shell for colon targeting. | 2001 Jan 29 |
|
Design and evaluation of microcapsules of diltiazem hydrochloride. | 2001 Jan-Feb |
|
[Parkinson syndrome from diltiazem]. | 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 |
|
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 |
|
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 angiotensin II on venodilator response to nitroglycerin. | 2001 Mar |
|
Differential efficacy of L- and T-type calcium channel blockers in preventing tachycardia-induced atrial remodeling in dogs. | 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 |
|
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 |
|
Calcium-channel antagonists and nitrates in coronary artery bypass patients receiving radial artery grafts. | 2001 May |
|
Trimetazidine for stable angina pectoris. | 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 |
|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/pro/dilt-cd.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7473567
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
Edited
Sat Dec 16 16:27:04 GMT 2023
by
admin
on
Sat Dec 16 16:27:04 GMT 2023
|
Record UNII |
EE92BBP03H
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
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 | ||
---|---|---|---|---|---|
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | ||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | ||
|
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 | |||
|
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 | |||
|
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 |
Related Record | Type | Details | ||
---|---|---|---|---|
|
SALT/SOLVATE -> PARENT |
|
||
|
BINDER->LIGAND |
|
||
|
TRANSPORTER -> SUBSTRATE | |||
|
TARGET -> INHIBITOR |
Binding assay
IC50
|
||
|
SALT/SOLVATE -> PARENT | |||
|
SALT/SOLVATE -> PARENT |
|
||
|
METABOLIC ENZYME -> INHIBITOR | |||
|
TRANSPORTER -> INHIBITOR | |||
|
TRANSPORTER -> INHIBITOR | |||
|
TARGET -> INHIBITOR |
BINDING
IC50
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLITE -> PARENT |
MINOR
URINE
|
||
|
METABOLITE -> PARENT |
MINOR
URINE
|
||
|
METABOLITE -> PARENT |
MINOR
URINE
|
||
|
METABOLITE -> PARENT |
In some plasma samples
MAJOR
URINE
|
||
|
METABOLITE -> PARENT |
MINOR
URINE
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
|