Molecular Structure of Duloxetine
Core Scaffold and Chemical Structure
Duloxetine is built on a thiophene-naphthalene core scaffold, specifically consisting of a naphthalene ring system linked through an oxygen atom to a thiophene ring, with a propylamine side chain. 1
The complete chemical designation is (+)-(S)-N-methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride, with the molecular formula C₁₈H₁₉NOS•HCl and a molecular weight of 333.88 g/mol. 1
Detailed Structural Components
Primary Scaffold Elements
- Naphthalene ring: The core aromatic system providing the primary hydrophobic scaffold 1
- Thiophene ring: A five-membered sulfur-containing heterocycle connected via an oxygen bridge to the naphthalene 1
- Propylamine chain: A three-carbon aliphatic chain terminating in a methylated amine group 1
Stereochemistry and Salt Form
- The molecule exists as the (S)-enantiomer, indicated by the (+) designation in the chemical name 1
- Duloxetine is formulated as the hydrochloride salt for pharmaceutical stability and solubility 1
- The hydrochloride salt appears as a white to brownish-white solid that is slightly soluble in water 1
Pharmacological Relevance of Structure
The thiophene-naphthalene scaffold is critical for duloxetine's dual mechanism as a balanced selective serotonin and norepinephrine reuptake inhibitor (SNRI). 1, 2 This structural framework allows the molecule to interact with both serotonin and norepinephrine transporters with relatively equal affinity, distinguishing it from other antidepressants. 3, 2
Formulation Considerations
The enteric-coated pellet formulation contains 20 mg, 30 mg, or 60 mg of duloxetine (equivalent to 22.4 mg, 33.7 mg, or 67.3 mg of duloxetine hydrochloride, respectively), designed specifically to prevent degradation in the acidic gastric environment. 1
Peer-Reviewed Sources and Official Databases
FDA Drug Label (Official): The complete structural information, molecular formula, and chemical designation are documented in the FDA-approved prescribing information for duloxetine delayed-release capsules 1
PubMed/MEDLINE Indexed Journals:
- American Journal of Health-System Pharmacy (2005) - comprehensive pharmacology review 2
- Clinical Pharmacokinetics (2011) - detailed pharmacokinetic analysis 4
- CNS Drugs (2007) - clinical pharmacology review 5
Chemical Structure Databases: The molecular structure can be verified through:
- PubChem (https://pubchem.ncbi.nlm.nih.gov/) - search CID 60835 for duloxetine
- ChemSpider (http://www.chemspider.com/) - Royal Society of Chemistry database
- DrugBank (https://go.drugbank.com/) - comprehensive drug database with structural data