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 |
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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 |
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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 |
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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 |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
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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. |
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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/ |
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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 |
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Antihypertensive efficacy and tolerability of once-daily sustained-release diltiazem alone and in combination with ramipril in hypertension. | 1999 Oct |
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Diltiazem causes open channel block of recombinant 5-HT3 receptors. | 1999 Sep 15 |
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[Unexpected formation of spiro(benzofuran-2,2'-(1,4)benzothiazines) from aurones]. | 2001 Apr |
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Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats. | 2001 Apr |
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Involvement of calcium signaling in the fibronectin-stimulated macrophage recognition of oxidatively damaged erythrocytes. | 2001 Apr 23 |
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Pharmacological interventions of cyanide-induced cytotoxicity and DNA damage in isolated rat thymocytes and their protective efficacy in vivo. | 2001 Feb 3 |
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Diltiazem affects human dendritic cell maturation. | 2001 Feb-Mar |
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Heart rate-lowering and -regulating effects of once-daily sustained-release diltiazem. | 2001 Jan |
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Design and evaluation of microcapsules of diltiazem hydrochloride. | 2001 Jan-Feb |
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Photostability and phototoxicity studies on diltiazem. | 2001 Jun |
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Inhibition by nifedipine of adherence- and activated macrophage-induced death of human gingival fibroblasts. | 2001 Mar 9 |
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Trimetazidine for stable angina pectoris. | 2001 May |
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Ca2+-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells. | 2001 May |
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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
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EE92BBP03H
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QC08DB01
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NBK547898
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C333
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SUB07148MIG
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Diltiazem
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DILTIAZEM
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C61725
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT |
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DERIVATIVE -> PARENT |
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LABELED -> NON-LABELED |
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BINDER->LIGAND |
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TARGET -> INHIBITOR |
Binding assay
IC50
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT |
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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METABOLIC ENZYME -> INHIBITOR | |||
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TARGET -> INHIBITOR |
BINDING
IC50
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MINOR
URINE
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METABOLITE -> PARENT |
MINOR
URINE
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METABOLITE -> PARENT |
MINOR
URINE
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METABOLITE -> PARENT |
In some plasma samples
MAJOR
URINE
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METABOLITE -> PARENT |
MINOR
URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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