Clotrimazole
[CAS# 23593-75-1]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antifungal drugs
• Name: Clotrimazole
• Synonyms: 1-((2-Chlorophenyl)diphenylmethyl)-1H-imidazole; 1-[(o-Chlorophenyl)diphenylmethyl]imidazole; 1-(o-Chlorotrityl)imidazole; Diphenyl-(2-chlorophenyl)-1-imidazolylmethane
• Molecular Formula: C₂₂H₁₇ClN₂
• Molecular Weight: 344.84
• CAS Registry Number: 23593-75-1
• EC Number: 245-764-8
• SMILES: C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3Cl)N4C=CN=C4

Properties

• Solubility: 75 mM (DMSO), 100mM (ethanol) (Expl.)
• Density: 1.1±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.617, Calc.^*
• Boiling Point: 482.3±40.0 °C (760 mmHg), Calc.^*
• Flash Point: 245.5±27.3 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H311-H315-H319-H361-H373-H400-H410
• Safety Statements: P203-P260-P262-P264-P264+P265-P270-P273-P280-P301+P317-P302+P352-P305+P351+P338-P316-P318-P319-P321-P330-P332+P317-P337+P317-P361+P364-P362+P364-P391-P405-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	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	3	H311
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Reproductive toxicity	Repr.	2	H361
Skin sensitization	Skin Sens.	1	H317
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332

Discovery and Applications

Clotrimazole is an antifungal medication primarily used for the treatment of fungal infections. It is a broad-spectrum antifungal agent belonging to the class of imidazole derivatives, which work by inhibiting the synthesis of ergosterol, an essential component of fungal cell membranes. The inhibition of ergosterol synthesis leads to an increase in cell membrane permeability, causing the death of the fungal cells.

Clotrimazole was first introduced in the 1960s and has since become one of the most commonly used topical antifungal agents. It is used in the treatment of various superficial fungal infections, including those caused by dermatophytes (such as *Trichophyton*, *Microsporum*, and *Epidermophyton* species), yeasts (such as *Candida* species), and other fungi that infect the skin, nails, and mucous membranes.

The medication is most commonly available in topical forms, such as creams, lotions, powders, and sprays, and is typically applied directly to the affected area of the skin. It is also available in vaginal preparations, such as suppositories and creams, to treat vaginal yeast infections caused by *Candida albicans*. Additionally, clotrimazole can be used in oral lozenges to treat oral thrush, another condition caused by *Candida* species. It can also be used to treat skin infections like athlete’s foot, jock itch, and ringworm.

One of the advantages of clotrimazole is its relatively low toxicity when applied topically, making it suitable for use in treating common fungal infections in both adults and children. However, its effectiveness is limited to superficial fungal infections, as it is not absorbed well into the bloodstream when applied topically. In more severe systemic fungal infections, other antifungal agents that are better absorbed or have a broader spectrum of activity may be used.

In addition to its antifungal properties, clotrimazole has been investigated for its potential to treat other conditions. Research has explored its use in cancer therapy, as it has been shown to have some effects on certain cancer cell lines, although these uses are still experimental and not widely adopted in clinical practice.

Clotrimazole is typically well tolerated, with side effects being relatively rare. However, some individuals may experience mild irritation, redness, or stinging at the site of application. Allergic reactions are also possible, though they are uncommon.

In conclusion, clotrimazole is an important antifungal medication used in the treatment of a variety of fungal infections, particularly those affecting the skin and mucous membranes. Its broad-spectrum antifungal activity and low toxicity profile make it a widely used and effective agent for treating superficial fungal infections.

References

1994. Treatment of superficial mycoses in the tropics: Whitfield's ointment versus clotrimazole. *International Journal of Dermatology*, 33(10).
DOI: 10.1111/j.1365-4362.1994.tb01524.x

1979. A comparison between the effects of nystatin, clotrimazole and miconazole on vaginal candidiasis. *BJOG: An International Journal of Obstetrics & Gynaecology*, 86(7).
DOI: 10.1111/j.1471-0528.1979.tb10812.x

1979. Superficial mycosis. Treatment with clotrimazole. Report of 60 cases. *Actas Dermo-Sifiliograficas*, 70(5-6).