Dapoxetine hydrochloride
[CAS# 129938-20-1]

Identification

• Classification: API >> Circulatory system medication >> Antihypertensive drug
• Name: Dapoxetine hydrochloride
• Synonyms: (1S)-N,N-Dimethyl-3-naphthalen-1-yloxy-1-phenyl-propan-1-amine hydrochloride
• Molecular Formula: C₂₁H₂₃NO.HCl
• Molecular Weight: 341.88
• CAS Registry Number: 129938-20-1
• EC Number: 640-411-8
• SMILES: CN(C)[C@@H](CCOC1=CC=CC2=CC=CC=C21)C3=CC=CC=C3.Cl

Properties

• Solubility: DMSO: 68 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H319-H413
• Safety Statements: P264-P264+P265-P270-P273-P280-P301+P317-P305+P351+P338-P330-P337+P317-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Serious eye damage	Eye Dam.	1	H318
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Skin irritation	Skin Irrit.	2	H315
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400

Discovery and Applications

Dapoxetine hydrochloride is the hydrochloride salt form of dapoxetine, a selective serotonin reuptake inhibitor (SSRI) primarily developed and used for the treatment of premature ejaculation (PE) in men. Chemically, dapoxetine hydrochloride is characterized by the presence of a naphthalene moiety linked to an amino group through a propyl chain, with the hydrochloride salt enhancing its solubility and stability. It appears as a white to off-white crystalline powder, soluble in water and polar organic solvents.

Dapoxetine was initially synthesized and investigated in the 1990s as an antidepressant due to its SSRI activity. However, during clinical development, it was discovered that dapoxetine has a rapid onset and short half-life compared to other SSRIs, properties that led to its repurposing for the treatment of premature ejaculation rather than depression. Its pharmacokinetic profile makes it suitable for on-demand use, distinguishing it from traditional SSRIs that require long-term administration.

The drug acts by inhibiting the serotonin transporter, which increases serotonin levels in the synaptic cleft. Elevated serotonin activity in certain areas of the central nervous system contributes to the delay of ejaculation by modulating ejaculatory reflexes. Dapoxetine’s rapid absorption and elimination allow for effective symptom control shortly after oral administration, usually within 1–3 hours, with a half-life of approximately 1.5 hours.

Clinically, dapoxetine hydrochloride is administered orally in tablet form, with doses typically ranging from 30 mg to 60 mg depending on patient response and tolerability. It is the first and only oral medication approved specifically for premature ejaculation in many countries, with a favorable safety and efficacy profile in clinical trials. Common side effects include nausea, headache, dizziness, and diarrhea, which are generally mild to moderate and transient.

Dapoxetine hydrochloride’s discovery and application represent an important advancement in sexual medicine, providing a pharmacological option for a condition that previously lacked effective oral treatments. The compound’s development followed rigorous preclinical and clinical studies to establish its safety, efficacy, and pharmacodynamics.

Handling and formulation of dapoxetine hydrochloride require standard pharmaceutical practices to ensure purity, stability, and bioavailability. The hydrochloride salt form is preferred for its enhanced solubility and ease of formulation into solid dosage forms.

In summary, dapoxetine hydrochloride is a selective serotonin reuptake inhibitor used primarily to treat premature ejaculation. It was initially developed as an antidepressant but repurposed due to its pharmacokinetic properties. The compound’s efficacy, rapid onset, and safety have made it a valuable medication in sexual health therapeutics.

References

2023. Dapoxetine prevents neuronal damage and improves functional outcomes in a model of ischemic stroke through the modulation of inflammation and oxidative stress. Naunyn-Schmiedeberg's Archives of Pharmacology, 397(3).
DOI: 10.1007/s00210-023-02601-7

2022. Determination of Dapoxetine Hydrochloride in Human Plasma by HPLC-MS/MS and Its Application in a Bioequivalence Study. Molecules (Basel, Switzerland), 27(9).
DOI: 10.3390/molecules27092707

2021. Investigation of the association complex formed between dapoxetine and erythrosine‐B for facile dapoxetine assay in pharmaceutical formulation using resonance Rayleigh scattering and spectrofluorimetric techniques. Luminescence : the journal of biological and chemical luminescence, 36(8).
DOI: 10.1002/bio.4133