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Showing drug card for Diltiazem (DB00343)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:32
Primary Accession Number DB00343
Secondary Accession Number
  • APRD00473
Name Diltiazem
Drug Type
  • Approved
  • Small Molecule
Description A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [PubChem]
Synonyms
  1. d-cis-Diltiazem
Brand Names
  1. Acalix
  2. Adizem
  3. Altiazem
  4. Anginyl
  5. Angizem
  6. Anoheal
  7. Apo-Diltiaz
  8. Britiazim
  9. Bruzem
  10. Calcicard
  11. Cardizem
  12. Cardizem CD
  13. Cardizem SR
  14. Cardizen LA
  15. Cartia XT
  16. Citizem
  17. Cormax
  18. Deltazen
  19. Dilacor
  20. Dilacor-XR
  21. Diladel
  22. Dilcontin
  23. Dilpral
  24. Dilrene
  25. Dilt-cd
  26. Dilta-Hexal
  27. Diltia
  28. Dilticard
  29. Dilzem
  30. Dilzen
  31. Endrydil
  32. Herbesser
  33. Incoril AP
  34. Masdil
  35. Novo-Diltazem
  36. Nu-Diltiaz
  37. Syn-Diltiazem
  38. Tiamate
  39. Tiazac
  40. Tiazac Tildiem
  41. Tiazac XC
  42. Viazem
Brand Mixtures Not Available
Chemical IUPAC Name [(2S,3S)-5-(2-dimethylaminoethyl)-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate
Chemical Formula C22H26N2O4S
Chemical Structure Structure
CAS Registry Number 42399-41-7
InChI Identifier InChI=1/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
InChI Key HSUGRBWQSSZJOP-RTWAWAEBBV
KEGG Drug Not Available
KEGG Compound C06958 Link Image
PubChem Compound 39186 Link Image
PubChem Substance 180243 Link Image
ChEBI ID Not Available
PharmGKB ID PA449334 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02244728 Link Image
RxList Link http://www.rxlist.com/cgi/generic/diltiaz.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/car1068.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Diltiazem Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference H. Kugita et al., U.S. Pat. 3,562,257 (1971)
Average Molecular Weight 414.5180
Monoisotopic Molecular Weight 414.1613
State Solid
Melting Point 231oC
Experimental Water Solubility 465 mg/L Source: PhysProp
Predicted Water Solubility 1.68e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.8 Source: PhysProp
Predicted LogP 3.09 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.39 Calculated using ALOGPS
Experimental Caco2 Permeability -4.38 [ADME Research, USCD]
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES COC1=CC=C(C=C1)[C@@H]1SC2=CC=CC=C2N(CCN(C)C)C(=O)[C@@H]1OC(C)=O
Canonical SMILES COC1=CC=C(C=C1)C1SC2=CC=CC=C2N(CCN(C)C)C(=O)C1OC(C)=O
Drug Category
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Calcium-channel blocking agents
  • Cardiovascular Agents
  • Vasodilator Agents
ATC Codes
AHFS Codes
  • 24:28.92
Indication For the treatment of Hypertension
Pharmacology Diltiazem, a benzothiazepine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Diltiazem is similar to other peripheral vasodilators. Diltiazem inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Mechanism of Action Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, dilitiazem, like verapamil, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.
Absorption Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect.
Toxicity LD50=740mg/kg (orally in mice)
Protein Binding 70%-80%
Biotransformation Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.
Half Life 3.0 - 4.5 hours
Dosage Forms
Form Route
Capsule, extended release Oral
Liquid Intravenous
Solution Intravenous
Tablet Oral
Tablet, extended release Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Amiodarone Increased risk of cardiotoxicity and arrhythmias
Amlodipine Increases the effect and toxicity of amlodipine
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Atazanavir Atazanavir increases the effect and toxicity of diltiazem
Atenolol Increased risk of bradycardia
Atorvastatin Increases the effect and toxicity of atorvastatin
Buspirone The calcium channel blocker increases the effect and toxicity of buspirone
Carbamazepine Increases the effect of carbamazepine
Cerivastatin Increases the effect and toxicity of the statin
Cilostazol Increases the effect of cilostazol
Cisapride Increases the levels of cisapride
Cyclosporine Increases the effect and toxicity of cyclosporine
Dihydroquinidine barbiturate Increases the effect and toxicity of quinidine
Lovastatin Increases the effect and toxicity of the statin
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Metoprolol Increased risk of bradycardia
Midazolam The calcium channel blocker increases the effect and toxicity of the benzodiazepine
Moricizine Increased effect/toxicity of moricizine
Pindolol Increased risk of bradycardia
Propranolol Increased risk of bradycardia
Quinidine Increases the effect and toxicity of quinidine
Quinidine barbiturate Increases the effect and toxicity of quinidine
Quinupristin This combination presents an increased risk of toxicity
Ranolazine Increased levels of ranolazine- risk of toxicity
Rifampin Rifampin decreases levels of diltiazem
Ritonavir Ritonavir increases diltiazem levels
Simvastatin Increases the effect and toicity of simvastatin
Sirolimus Increases the effect and toxicity of sirolimus
Tacrolimus Increases levels of tacrolimus
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Triazolam The calcium channel blocker increases the effect and toxicity of the benzodiazepine
Food Interactions
  • Avoid natural licorice.
  • Take this medication 30 minutes before meals.
Pathways
Name SMPDB Link KEGG Link
Diltiazem Pathway SMP00359 Link Image
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
  4. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C19 (CYP2C19)
  2. Cytochrome P450 3A4 (CYP3A4)
  3. Cytochrome P450 2D6 (CYP2D6)
Targets
  1. Voltage-dependent calcium channel gamma-1 subunit
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C19 (CYP2C19)
Enzyme 1 Gene Name CYP2C19
Enzyme 1 SwissProt ID P33261 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P33261|CP2CJ_HUMAN Cytochrome P450 2C19 (EC 1.14.13.80) 
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI
YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM
ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID
LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK
KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP
PFYQLCFIPV
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 2 Gene Name CYP3A4
Enzyme 2 SwissProt ID P08684 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 3 Gene Name CYP2D6
Enzyme 3 SwissProt ID P10635 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1) 
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Drug Target 1 [top]
Target 1 ID 750
Target 1 Name Voltage-dependent calcium channel gamma-1 subunit
Target 1 Synonyms
  1. Dihydropyridine- sensitive L-type, skeletal muscle calcium channel subunit gamma
Target 1 Gene Name CACNG1
Target 1 Protein Sequence >Voltage-dependent calcium channel gamma-1 subunit 
MSQTKMLKVRVTLFCILAGIVLAMTAVVTDHWAVLSPHMEHHNTTCEAAHFGLWRICTKR
IPMDDSKTCGPITLPGEKNCSYFRHFNPGESSEIFEFTTQKEYSISAAAIAIFSLGFIIL
GSLCVLLSLGKKRDYLLRPASMFYAFAGLCILVSVEVMRQSVKRMIDSEDTVWIEYYYSW
SFACACAAFILLFLGGLALLLFSLPRMPRNPWESCMDAEPEH
Target 1 Number of Residues 225
Target 1 Molecular Weight 25029
Target 1 Theoretical pI 7.10
Target 1 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
voltage-gated ion channel activity
voltage-gated calcium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
di-, tri-valent inorganic cation transport
calcium ion transport
Component
intrinsic to membrane
integral to membrane
cell
membrane
Target 1 General Function Involved in voltage-gated calcium channel activity
Target 1 Specific Function This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 11-29
  • 105-129
  • 140-155
  • 180-204
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 306473 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q06432 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name CCG1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >669 bp 
ATGTCCCAGACCAAAATGCTGAAGGTCCGCGTGACCCTCTTCTGCATCCTGGCAGGCATC
GTGCTGGCCATGACAGCCGTGGTAACCGACCACTGGGCTGTGCTGAGCCCCCACATGGAG
CACCACAACACTACCTGCGAGGCGGCCCACTTCGGCCTCTGGCGGATTTGTACCAAGCGC
ATCCCCATGGACGACAGCAAGACCTGCGGGCCCATCACCCTGCCCGGGGAGAAGAACTGT
TCCTACTTCAGGCATTTTAACCCCGGCGAGAGCTCGGAGATCTTCGAATTCACCACTCAG
AAGGAGTACAGCATCTCGGCAGCCGCCATCGCCATCTTCAGCCTTGGCTTCATCATCCTG
GGCAGCCTCTGTGTCCTCCTGTCCCTCGGGAAGAAGAGGGACTATCTGCTGCGACCCGCG
TCCATGTTCTATGCCTTTGCAGGTCTCTGCATCCTCGTCTCGGTGGAGGTCATGCGGCAG
TCGGTGAAGCGCATGATTGACAGTGAGGACACCGTCTGGATCGAGTACTATTACTCCTGG
TCCTTTGCCTGCGCCTGTGCCGCCTTCATCCTCCTCTTTCTCGGCGGTCTCGCCCTCCTG
CTGTTCTCCCTGCCTCGAATGCCCCGGAACCCATGGGAGTCCTGCATGGATGCTGAGCCC
GAGCACTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID CACNG1 Link Image
Target 1 GenAtlas ID CACNG1 Link Image
Target 1 HGNC ID HGNC:1405 Link Image
Target 1 Chromosome Location 17
Target 1 Locus 17q24
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Powers PA, Liu S, Hogan K, Gregg RG: Molecular characterization of the gene encoding the gamma subunit of the human skeletal muscle 1,4-dihydropyridine-sensitive Ca2+ channel (CACNLG), cDNA sequence, gene structure, and chromosomal location. J Biol Chem. 1993 May 5;268(13):9275-9. [PubMed Link Image]
  2. Iles DE, Segers B, Weghuis DO, Suikerbuijk R, Wieringa B: Localization of the gamma-subunit of the skeletal muscle L-type voltage-dependent calcium channel gene (CACNLG) to human chromosome band 17q24 by in situ hybridization and identification of a polymorphic repetitive DNA sequence at the gene locus. Cytogenet Cell Genet. 1993;64(3-4):227-30. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.