| 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 |
|
| Name |
Diltiazem |
| Drug Type |
|
| 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 |
- d-cis-Diltiazem
|
| Brand Names |
- Acalix
- Adizem
- Altiazem
- Anginyl
- Angizem
- Anoheal
- Apo-Diltiaz
- Britiazim
- Bruzem
- Calcicard
- Cardizem
- Cardizem CD
- Cardizem SR
- Cardizen LA
- Cartia XT
- Citizem
- Cormax
- Deltazen
- Dilacor
- Dilacor-XR
- Diladel
- Dilcontin
- Dilpral
- Dilrene
- Dilt-cd
- Dilta-Hexal
- Diltia
- Dilticard
- Dilzem
- Dilzen
- Endrydil
- Herbesser
- Incoril AP
- Masdil
- Novo-Diltazem
- Nu-Diltiaz
- Syn-Diltiazem
- Tiamate
- Tiazac
- Tiazac Tildiem
- Tiazac XC
- 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 |
 |
| 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  |
| PubChem Compound |
39186  |
| PubChem Substance |
180243  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA449334  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02244728  |
| RxList Link |
http://www.rxlist.com/cgi/generic/diltiaz.htm  |
| PDRhealth Link |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/car1068.shtml  |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Diltiazem  |
| 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 | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 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 |
|
| 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  |
| Contraindications |
Show  |
| Interactions |
Show  |
| 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  |
|
|
| General References |
- Drugs.com

- Wikipedia

- RxList

- PDRhealth

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 2C19 (CYP2C19)
- Cytochrome P450 3A4 (CYP3A4)
- Cytochrome P450 2D6 (CYP2D6)
|
| Targets |
- 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  |
| Enzyme 1 SNPs |
SNPJam Report  |
| 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  |
| Enzyme 2 SNPs |
SNPJam Report  |
| 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  |
| Enzyme 3 SNPs |
SNPJam Report  |
| 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 |
- 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 |
|
| Target 1 Transmembrane Regions |
- 11-29
- 105-129
- 140-155
- 180-204
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
306473  |
| Target 1 UniProtKB/Swiss-Prot ID |
Q06432  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
CCG1_HUMAN  |
| 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  |
| Target 1 GenAtlas ID |
CACNG1  |
| Target 1 HGNC ID |
HGNC:1405  |
| Target 1 Chromosome Location |
17 |
| Target 1 Locus |
17q24 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- 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
]
- 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
]
|
| Target 1 Drug References |
- 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
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|