Terbinafine hydrochloride
[CAS# 78628-80-5]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antifungal drugs
• Name: Terbinafine hydrochloride
• Synonyms: (E)-N-(6,6-Dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine monohydrochloride
• Molecular Formula: C₂₁H₂₅N.HCl;C₂₁H₂₆ClN
• Molecular Weight: 327.90
• CAS Registry Number: 78628-80-5
• EC Number: 616-640-4
• SMILES: CC(C)(C)C#C/C=C/CN(C)CC1=CC=CC2=CC=CC=C21.Cl

Properties

• Melting point: 214 °C (Expl.)
• Solubility: DMSO 10 mg/ml Ethanol 30 mg/ml (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS09 Warning
• Risk Statements: H315-H319-H335-H400-H410
• Safety Statements: P261-P264-P264+P265-P271-P273-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H312
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - repeated exposure	STOT RE	1	H372

Discovery and Applications

Terbinafine hydrochloride is the hydrochloride salt form of terbinafine, a synthetic antifungal agent widely used in the treatment of dermatophytic infections, including conditions such as athlete's foot, ringworm, and onychomycosis (fungal infections of the nails). It belongs to the class of allylamine antifungals and works by inhibiting the synthesis of ergosterol, a vital component of the fungal cell membrane.

The discovery of terbinafine dates back to the 1980s when it was developed by the pharmaceutical company Novartis (formerly Ciba-Geigy). Initially, it was designed to target the enzymes involved in sterol biosynthesis in fungi. Its mechanism of action is based on its ability to selectively inhibit squalene epoxidase, an enzyme crucial for the synthesis of ergosterol. By disrupting the production of ergosterol, a major component of fungal cell membranes, terbinafine causes the accumulation of squalene, which is toxic to the fungus. This results in the death of the fungal cell.

Terbinafine is effective against a variety of fungi, including dermatophytes, which are responsible for most superficial skin infections. It is also effective against certain yeasts and molds, though its primary clinical use is for treating dermatophyte infections. The drug can be administered orally or topically, depending on the severity and location of the infection. For superficial fungal infections, topical application in the form of creams, gels, or sprays is common. For more extensive or nail infections, oral administration of terbinafine hydrochloride is often recommended.

One of the key advantages of terbinafine is its relatively long duration of action, allowing for shorter treatment courses compared to other antifungal agents. For example, the oral formulation of terbinafine is typically administered for 2 to 6 weeks for toenail infections, compared to several months of treatment with other antifungal drugs like itraconazole or griseofulvin. This shorter treatment regimen is beneficial for improving patient compliance.

The clinical effectiveness of terbinafine hydrochloride has been well established through numerous studies and clinical trials. It is considered a first-line treatment for dermatophyte infections, particularly onychomycosis, due to its proven efficacy and safety profile. In addition to its antifungal action, terbinafine has a relatively low incidence of side effects. The most common side effects include gastrointestinal disturbances, such as nausea, diarrhea, and abdominal pain. More serious side effects, including liver toxicity, are rare but can occur, necessitating periodic liver function monitoring during prolonged treatment.

Terbinafine hydrochloride's popularity in clinical practice is further reinforced by its relatively low risk of drug interactions compared to other antifungal agents. It is metabolized primarily in the liver by the cytochrome P450 enzyme system, specifically CYP2D6. While terbinafine does not significantly interact with most other medications, caution is recommended when it is used concurrently with drugs that affect the CYP450 system, as this may influence its metabolism and increase the risk of side effects.

In conclusion, terbinafine hydrochloride is a widely used and highly effective antifungal agent for the treatment of various dermatophyte infections. Its selective action against fungal cell membrane synthesis, combined with a favorable safety profile and relatively short treatment duration, makes it an essential tool in modern dermatology. Ongoing research continues to explore its use in treating other fungal infections, further expanding its therapeutic potential.

References

1998. Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers. Antimicrobial Agents and Chemotherapy, 42(3).
DOI: 10.1128/aac.42.3.695

2005. In vitro activities of posaconazole, ravuconazole, terbinafine, itraconazole and fluconazole against dermatophyte, yeast and non-dermatophyte species. Medical Mycology, 43(2).
DOI: 10.1080/13693780410001731583

2024. Systemic absorption and safety of topical terbinafen hydrochloride 10% solution (MOB015B): a phase 1 maximal usage trial in patients with moderate-to-severe onychomycosis. Antimicrobial Agents and Chemotherapy.
DOI: 10.1128/aac.00682-24