General
Preferred name
diltiazem
Synonyms
DILTIAZEM HYDROCHLORIDE ()
CRD-401 ()
Diltiazem HCl ()
RG 83606 HCl ()
(+)-CIS-DILTIAZEM HYDROCHLORIDE ()
Diltiazem (hydrochloride) ()
Angiotrofin ()
Dilzem SR 60 ()
Dilrene ()
Tildiem ()
Dilzem SR 120 ()
Slozem 240 ()
Calazem ()
Masdil ()
Zilden ()
RG 83606 ()
Kentiazem ()
Horizem SR 90 ()
Dilcardia SR ()
Angiozem CR 120 ()
Bi-Carzem XL ()
Slozem 120 ()
Zemtard 300 XL ()
Uard 240XL ()
Angitil XL 240 ()
Dilzem SR 90 ()
Kenzem SR ()
Tiazac ()
Zildil SR ()
Anoheal ()
Tildiem LA 200 ()
Angitil XL 300 ()
Calcicard ()
Optil SR 180 ()
Dilpral ()
Horizem SR 60 ()
Adizem ()
Optil SR 90 ()
Viazem XL ()
Diladel ()
Zemtard 240 XL ()
Adizem-60 ()
Tildiem LA 300 ()
RG-83606 ()
Taztia Xt ()
Angitil SR 180 ()
Adizem-XL ()
Cardizem La ()
Adizem-SR ()
Angitil SR 90 ()
Uard 180XL ()
Dilzem XL 120 ()
Angitil SR 120 ()
Angiozem 60 ()
Zemtard 120 XL ()
Optil XL 240 ()
Optil SR 120 ()
Cartia ()
Retalzem 60 ()
Tildiem Ret 120 ()
Cardizem Cd ()
Disogram SR ()
Dilzene ()
Slozem 180 ()
Horizem SR 120 ()
Dilcardia XL ()
Uard 300XL ()
Taztia ()
Cartia Xt ()
Diltzac ()
Zemtard 180 XL ()
Zemret 180 XL ()
Cardizem Sr ()
Bi-Carzem SR ()
Dilacor Xr ()
Altiazem ()
Dilt-Cd ()
Zemret 300 XL ()
Zemret 240 XL ()
Diltiazem hydrochloride in dextrose 5% ()
Optil XL 300 ()
Calcicard CR ()
Uard 120XL ()
Cardizem ()
Dilzem ()
Britiazim ()
Angiozem CR 90 ()
Dilzem XL 240 ()
NSC-759576 ()
Tiamex ()
Deltazen ()
Slozem ()
Optil ()
Tildiem Ret 90 ()
Dilzem XL 180 ()
Ditiaz ()
Surazem ()
Tiamate ()
Diltiazem extended release ()
MK-793 ()
DILTIAZEM MALATE ()
P&D ID
PD010090
CAS
33286-22-5
42399-41-7
144604-00-2
103532-26-9
56209-45-1
Tags
available
natural product
drug
Approved by
FDA
First approval
1996
1982
Drug indication
Antihypertensive
Vasodilator (coronary)
Hypertension
Antihypertensive,Vasodilator (coronary)
Drug Status
investigational
approved
Max Phase
4.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE Due to its extensive metabolism, only 2% to 4% of the unchanged drug can be detected in the urine.[label]
PHARMACODYNAMICS Diltiazem is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.[label] Diltiazem inhibits the influx of extracellular calcium ions across the myocardial and vascular smooth muscle cell membranes during depolarization. Diltiazem is classified as a negative inotrope (decreased force) and negative chronotrope (decreased rate).[L6289] It is also considered a rate-control drug as it reduces heart rate.[A178432,T28] Diltiazem is exerts hemodynamic actions by reducing blood pressure, systemic vascular resistance, the rate-pressure product, and coronary vascular resistance while increasing coronary blood flow.[L6292] Diltiazem decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations.[label] In supraventricular tachycardia, diltiazem prolongs AV nodal refractories.[L6292]; ; As the magnitude of blood pressure reduction is related to the degree of hypertension, the antihypertensive effect of diltiazem is most pronounced in individuals with hypertension.[label] In a randomized, double-blind, parallel-group, dose-response study involving patients with essential hypertension, there was a reduction in the diastolic blood pressure by 1.9, 5.4, 6.1, and 8.6 mmHg in the patients receiving diltiazem at doses of 120, 240, 360, and 540 mg, respectively. In patients receiving placebo, there was a reduction in the diastolic blood pressure by 2.6 mmHg.[label] In a randomized, double-blind study involving patients with chronic stable angina, variable doses of diltiazem administered at night all caused an increased exercise tolerance in the after 21 hours, compared to placebo.[label] In the NORDIL study of patients with hypertension, the therapeutic effectiveness of diltiazem in reducing cardiovascular morbidity and mortality was assessed.[A178432] When using the combined primary endpoint as fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death, fatal and non-fatal stroke was shown to be reduced by 25% in the diltiazem group. Although the clinical significance to this effect remains unclear, it is suggested that diltiazem may exert a protective role against cerebral stroke in hypertensive patients.[A178432]
ABSORPTION Diltiazem is readily absorbed from the gastrointestinal tract. Minimum therapeutic plasma diltiazem concentrations appear to be in the range of 50 to 200 ng/mL.[label] Following oral administration of extended formulations of 360 mg diltiazem, the drug in plasma was detectable within 3 to 4 hours and the peak plasma concentrations were reached between 11 and 18 hours post-dose. Diltiazem peak and systemic exposures were not affected by concurrent food intake.[label] Due to hepatic first-pass metabolism, the absolute bioavailability following oral administration is about 40%[label], with the value ranging from 24 to 74% due to high interindividual variation in the first pass effect.[A178420] The bioavailability may increase in patients with hepatic impairment.[label]
DESCRIPTION Diltiazem has vasodilating actions. (GtoPdb)
INDICATION **Oral**; ; Indicated for the management of hypertension, to lower blood pressure, alone or in combination with other antihypertensive agents.[label]; ; Indicated for use to improve exercise tolerance in patients with chronic stable angina.[label]; ; Indicated for the management of variant angina (Prinzmetal's angina).[L6298]; ; **Intravenous**; ; Indicated for the short-term management of atrial fibrillation or atrial flutter for temporary control of rapid ventricular rate.[L6292]; ; Indicated for the rapid conversion of paroxysmal supraventricular tachycardias (PSVT) to sinus rhythm. This includes AV nodal reentrant tachycardias and reciprocating tachycardias associated with an extranodal accessory pathway such as the WPW syndrome or short PR syndrome.[L6292]; ; **Off-label**; ; Indicated for off-label uses in anal fissures (as topical formulation), migraine prophylaxis, cramps in lower leg related to rest, pulmonary hypertension,[L6289] idiopathic dilated cardiomyopathy, and proteinuria associated with diabetic nephropathy.[L6298]
METABOLISM Diltiazem is subject to extensive first-pass metabolism, which explains its relatively low absolute oral bioavailability. It undergoes metabolism primarily mediated by CYP3A4. Diltiazem is reported to undergo deacetylation, N- demethylation, and O-demethylation, as well as conjugation reactions mediated by CYP450 enzymes, with CYP3A4 being the primary enzyme responsible for drug metabolism. Metabolites N-monodesmethyldiltiazem, desacetyldiltiazem, desacetyl-N-monodesmethyldiltiazem, desacetyl-O- desmethyldiltiazem, and desacetyl-N, O-desmethyldiltiazem have been identified in human urine.[L6292] It is proposed that N-desmethyldiltiazem, deacetyldiltiazem, deacetyl-N-monodesmethyldiltiazem, and desacetyl-O- desmethyldiltiazem all retain pharmacological activity with varying potency.[A178516] Desacetyldiltiazem is present in the plasma at levels of 10% to 20% of the parent drug and retains about 25-50% of the pharmacological activity to that of the parent compound.[label] Radioactivity studies indicate the presence of other metabolites that persist in the plasma for 20 hours, compared to diltiazem that is detectable for 2 to 5 hours.[label]
HALF-LIFE The plasma elimination half-life is approximately 3.0 - 4.5 hours following single and multiple oral doses. The half-life may slightly increase with dose and the extent of hepatic impairment.[label] The apparent elimination half-life for diltiazem as extended-release tablets after single or multiple dosing is 6 to 9 hours.[label] The plasma elimination half-life is approximately 3.4 hours following administration of a single intravenous injection.[L6292]
DESCRIPTION NMDA antagonist; acts at glycine site (Tocris Bioactive Compound Library)
DESCRIPTION Ca2+ channel blocker (L-type) (Tocriscreen Plus)
DESCRIPTION Ca2+ channel antagonist selective for slow, or L-type, channels; stimulates 1,4-dihydropyridine binding to Ca2+ channels; coronary vasodilator (LOPAC library)
DESCRIPTION Ca2+ channel blocker (L-type) (Tocriscreen Total)
Cell lines
0
Organisms
5
Compound Sets
36
AdooQ Bioactive Compound Library
A10311
Axon Medchem Screening Library
3323
Cayman Chemical Bioactives
20079
ChEMBL Approved Drugs
CHEMBL1697
CHEMBL23
CHEMBL1200805
ChEMBL Drugs
CHEMBL1697
CHEMBL23
CHEMBL1200805
Concise Guide to Pharmacology 2017/18
2298
Concise Guide to Pharmacology 2019/20
2298
Concise Guide to Pharmacology 2021/22
2298
Concise Guide to Pharmacology 2023/24
2298
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB00343
DrugBank Approved Drugs
DB00343
DrugCentral
897
DrugCentral Approved Drugs
897
DrugMAP
DMAI7ZV
DrugMAP Approved Drugs
DMAI7ZV
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS100735
Guide to Pharmacology
2298
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL23
Mcule NIBR MoA Box Subset
MCULE-4619243453
MedChem Express Bioactive Compound Library
HY-14656
HY-B0632
NCATS Inxight Approved Drugs
EE92BBP03H
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Diltiazem-HCl(Tiazac)
TargetMol Bioactive Compound Library
T0112
Tocris Bioactive Compound Library
0685
Tocriscreen Plus
0685
Tocriscreen Total
ZINC Tool Compounds
ZINC000000621893
External IDs
93
Properties
(calculated by RDKit )
Molecular Weight
414.16
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
0
Rotatable Bonds
6
Ring Count
3
Aromatic Ring Count
2
cLogP
3.37
TPSA
59.08
Fraction CSP3
0.36
Chiral centers
2.0
Largest ring
7.0
QED
0.68
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Ion Channels
Selectivity
L-type
Pathway
Membrane Transporter/Ion Channel
Neuronal Signaling
Target
Calcium Channel
CACNA1C, CACNA1S, CACNA2D1, CACNG1, HTR3A, KCNA5
Ca channel antagonist
Primary Target
CaV1.x Channels (L-type)
MOA
Blocker
L-Type Calcium Channel Blockers
calcium channel blocker
Member status
member
Indication
hypertension, angina pectoris
Therapeutic Class
Antihypertensive Agents
Source data