Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C22H26N2O4S.C4H4O4 |
Molecular Weight | 530.59 |
Optical Activity | ( + ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.COC1=CC=C(C=C1)[C@@H]2SC3=CC=CC=C3N(CCN(C)C)C(=O)[C@@H]2OC(C)=O
InChI
InChIKey=WHBXLOWLFLTDMD-WECFPGDBSA-N
InChI=1S/C22H26N2O4S.C4H4O4/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;5-3(6)1-2-4(7)8/h5-12,20-21H,13-14H2,1-4H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t20-,21+;/m1./s1
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 |
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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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Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect. | 2000 Jan |
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Oral amiodarone increases the efficacy of direct-current cardioversion in restoration of sinus rhythm in patients with chronic atrial fibrillation. | 2000 Jan |
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Diltiazem-mediated inhibition of sildenafil metabolism may promote nitrate-induced hypotension. | 2000 Oct |
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Physiology in medicine: importance of hypoxic pulmonary vasoconstriction in maintaining arterial oxygenation during acute respiratory failure. | 2001 |
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Influence of diltiazem on the pharmacokinetics of amlodipine in elderly hypertensive patients. | 2001 Apr |
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Atrial fibrillation: is rate stabilization a valid clinical strategy? | 2001 Apr |
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An extremely severe case of cutaneous calcinosis with juvenile dermatomyositis, and successful treatment with diltiazem. | 2001 Apr |
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Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs. | 2001 Apr |
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Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats. | 2001 Apr |
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Drug release from and mechanical properties of press-coated tablets with hydroxypropylmethylcellulose acetate succinate and plasticizers in the outer shell. | 2001 Apr 17 |
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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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Susac's syndrome: beneficial effects of corticosteroid therapy in a Japanese case. | 2001 Feb |
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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 |
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Diltiazem-associated photodistributed hyperpigmentation: a review of 4 cases. | 2001 Feb |
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Acute ventricular rate control in atrial fibrillation: IV combination of diltiazem and digoxin vs. IV diltiazem alone. | 2001 Feb |
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Mechanical stress stimulates phospholipase C activity and intracellular calcium ion levels in neonatal rat cardiomyocytes. | 2001 Feb |
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Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells. | 2001 Feb |
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Calcium antagonists as inhibitors of in vitro low density lipoprotein oxidation and glycation. | 2001 Feb 1 |
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Diltiazem downregulates IL-12 production by human dendritic cells. | 2001 Feb-Mar |
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Diltiazem affects human dendritic cell maturation. | 2001 Feb-Mar |
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Muscarinic activation of transient inward current and contraction in canine colon circular smooth muscle cells. | 2001 Jan |
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Heart rate-lowering and -regulating effects of once-daily sustained-release diltiazem. | 2001 Jan |
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Prehospital management of rapid atrial fibrillation: recommendations for treatment protocols. | 2001 Jan |
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Protein kinase C activates store-operated Ca(2+) channels in human glomerular mesangial cells. | 2001 Jul 13 |
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Na+ effects on mitochondrial respiration and oxidative phosphorylation in diabetic hearts. | 2001 Jun |
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Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias. | 2001 Jun |
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Electrophysiological characteristics of rat gustatory cyclic nucleotide--gated channel expressed in Xenopus oocytes. | 2001 Jun |
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Photostability and phototoxicity studies on diltiazem. | 2001 Jun |
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Analysis of multicomponent formulations containing phenylpropanolamine hydrochloride, caffeine and diazepam by using LC. | 2001 Jun |
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Adsorptive stripping voltammetric determination of antihypertensive agent: diltiazem. | 2001 Jun |
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cAMP modulates the excitability of immortalized H=hypothalamic (GT1) neurons via a cyclic nucleotide gated channel. | 2001 Jun |
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Smooth muscle relaxation and local hydraulic impedance properties of the aorta. | 2001 Jun |
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Calcium signaling pathways utilized by P2X receptors in freshly isolated preglomerular MVSMC. | 2001 Jun |
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Contraction of human colonic circular smooth muscle cells is inhibited by the calcium channel blocker pinaverium bromide. | 2001 Jun |
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An alternative method to the evaluation of similarity factor in dissolution testing. | 2001 Jun 4 |
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Clinical outcomes of aneurysmal subarachnoid hemorrhage patients treated with oral diltiazem and limited intensive care management. | 2001 Mar |
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Positive and negative contractile effects of somatostatin-14 on rat ventricular cardiomyocytes. | 2001 Mar |
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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 |
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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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Heart rate-lowering calcium antagonists in hypertensive post-myocardial infarction patients. | 2001 May |
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Inhibitory effects of TA-993 and its metabolite MB3 on platelet activation induced by collagen and U-46619 in human platelets. | 2001 May |
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Dilitiazem reduces nitric oxide production by human immune cells. | 2001 May |
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Randomized trial of rhythm or rate control in atrial fibrillation: the Pharmacological Intervention in Atrial Fibrillation Trial (PIAF). | 2001 May |
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Diltiazem treatment does not alter renal function after thoracic surgery. | 2001 May |
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Calcium-channel antagonists and nitrates in coronary artery bypass patients receiving radial artery grafts. | 2001 May |
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Left ventricular diastolic heart failure with normal left ventricular systolic function in older persons. | 2001 May |
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[Attempted suicide with sustained release diltiazem]. | 2001 May 12 |
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.
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67938926
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139492-78-7
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DBSALT002322
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896626Q8XW
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314592
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PRIMARY | RxNorm |
ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD