Diltiazem |
![]() Last updated: 07/09/2025 |
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(Also known as: d-cis-diltiazem ) |
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A non-dihydropyridine (non-DHP) veterinary drug usually formulated as the hydrochloride | |
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Used in the treatment of atrial fibrillation, supraventricular tachycardias, hypertrophic cardiomyopathy and hypertension | |
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Dogs; Cats |
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Approved - usually available as a prescription only medicine to be authorised by a veterinarian (POM-V) | |
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Approved |
Chemical structure |
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Diltiazem exhibits stereoisomerism, specifically optical and geometric isomerism, due to the presence of two chiral centres at the 2nd and 3rd carbon atoms of its benzothiazepine ring system. These chiral centres allow for the formation of four stereoisomers: two pairs of enantiomers that exist in either cis or trans configurations depending on the spatial arrangement of substituents around the ring. The therapeutically active form is the (2S,3S)-cis isomer, commonly referred to as d-cis-diltiazem hydrochloride. | |
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C₂₂H₂₆N₂O₄S | |
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CC(=O)OC1C(SC2=CC=CC=C2N(C1=O)CCN(C)C)C3=CC=C(C=C3)OC | |
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CC(=O)O[C@@H]1[C@@H](SC2=CC=CC=C2N(C1=O)CCN(C)C)C3=CC=C(C=C3)OC | |
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HSUGRBWQSSZJOP-RTWAWAEBSA-N | |
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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 | |
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Yes |
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Common Name | Relationship | Link |
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diltiazem | - | ![]() |
General status |
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Vasodilator, Medicinal drug | |
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Unclassified substance | |
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Synthetic | |
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A calcium channel blocker | |
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[Voltage-dependent calcium channel gamma-1 subunit, Antagonist] | |
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42399-41-7 | |
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255-796-4 | |
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Cardiobascular system: Calcium channel blockers | |
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QC08DB01 | |
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No | |
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414.52 | |
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cis-(+)-[2-(2-dimethylaminoethyl)-5-(4-methoxyphenyl)-3-oxo-6-thia-2-azabicyclo[5.4.0]undeca-7,9,11-trien-4-yl]ethanoate | |
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White crystalline powder | |
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Commercial |
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Generally formulated as oral tablets using the hydrochloride salt | |||||||||
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The production of diltiazem involves a multi-step chemical synthesis beginning with the condensation of 4-methoxybenzaldehyde and methyl chloroacetate under Darzens reaction conditions to form a glycidylic acid ester. This intermediate undergoes epoxide ring opening with 2-aminothiophenol, yielding a propionic acid derivative. After hydrolysis, the resulting racemic acid is resolved using (+)-alpha-phenylethylamine to isolate the desired stereoisomer. Cyclisation of this compound in a mixture of acetic anhydride, dimethylformamide, and pyridine forms the benzothiazepine ring and acylates the hydroxyl group. Finally, alkylation with 2-dimethylaminoethyl chloride completes the synthesis of diltiazem, specifically the (2S,3S)-cis isomer, which is pharmacologically active. | |||||||||
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Published GHG data is not available for most pharmaceuticals. However, according to industry, global averages suggest producing 1 kg of a typical active pharmaceutical ingredient can range from 10 to 100 kg CO₂e for small molecule drugs and potentially up to 1000 kg CO₂e for complex biologicals such as vaccines, depending on the drug type, its formulation, complexity of synthesis, solvent recovery, and energy sources used. |
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465 | V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source |
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231 | F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data |
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Decomposes before boiling | V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source |
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212 | V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source |
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6.17 X 1002 | Calculated | - | |||||||
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2.79 | R4 R = Peer reviewed scientific publications 4 = Verified data |
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8.90 | R4 R = Peer reviewed scientific publications 4 = Verified data |
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Degradation |
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As this parameter is not normally measured directly, a surrogate measure is used: ‘Photochemical oxidative DT₅₀’. Where data is available, this can be found in the Fate Indices section below. | ||||||||||
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Soil adsorption and mobility |
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Fate indices |
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Known soil and groundwater metabolites |
None
Other known metabolites |
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N-demethyldiltiazem | - | Human (Liver) | - | ||||
deacetyldiltiazem | - | Human | - | ||||
desacetyldiltiazem | - | Human | - |
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Terrestrial ecotoxicology |
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740 | F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) Mouse4 = Verified data |
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Aquatic ecotoxicology |
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15.0 | R4 R = Peer reviewed scientific publications Oryzias latipes4 = Verified data |
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28.0 | R4 R = Peer reviewed scientific publications Daphnia magna4 = Verified data |
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General |
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High (class III) | - | - | ||||||||
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740 | F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) Mouse4 = Verified data |
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Intraperitoneal LDLo = 220 mg kg⁻¹ | V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) Mouse3 = Unverified data of known source |
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Intravenous LD₅₀ = 61 mg kg⁻¹ | V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) Mouse3 = Unverified data of known source |
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Metabolised in the liver and excreted in the urine | A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications ) 5 = Verified data used for regulatory purposes |
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Health issues |
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May cause anorexia, vomiting, diarrhoea, abdominal pain, paralytic ileus and dyspepsia Teratogenic |
Handling issues |
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No information available | |||
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Not listed (Not listed) | |||
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diltiazem | ||
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Record last updated: | 07/09/2025 |
Contact: | aeru@herts.ac.uk |
Please cite as: | Lewis, K.A., Tzilivakis, J., Warner, D. and Green, A. (2016) An international database for pesticide risk assessments and management. Human and Ecological Risk Assessment: An International Journal, 22(4), 1050-1064. DOI: 10.1080/10807039.2015.1133242 |