Terbinafine: mode of action and properties of the squalene epoxidase inhibition.

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Ryder NS

Terbinafine: mode of action and properties of the squalene epoxidase inhibition.

Br J Dermatol. 1992 Feb;126 Suppl 39:2-7.

PubMed ID

1543672 [ View in PubMed

]

Abstract

Terbinafine (Lamisil) has primarily fungicidal action against many fungi as a result of its specific mechanism of squalene epoxidase inhibition. Treated fungi accumulate squalene while becoming deficient in ergosterol, an essential component of fungal cell membranes. The cidal action is closely associated with the development of high intracellular squalene concentrations, which are believed to interfere with fungal membrane function and cell wall synthesis. In the case of Candida albicans, growth inhibition with terbinafine appears to result from the ergosterol deficiency. The filamentous form of this fungus is more susceptible than the yeast form. Measurement of ergosterol biosynthesis by incorporation of radiolabelled precursors indicates a correlation between inhibition of growth and ergosterol biosynthesis in a range of pathogenic fungi. Terbinafine is a potent non-competitive inhibitor of squalene epoxidase from Candida (Ki = 30 nM). In contrast, inhibition of rat liver squalene epoxidase only occurs at higher drug concentrations (Ki = 77 microM), and is competitive with squalene. Thus, terbinafine has no effect on cholesterol biosynthesis in vivo. Squalene epoxidase is not an enzyme of the cytochrome P-450 type, thereby avoiding potential inhibition of this class of enzymes.

DrugBank Data that Cites this Article

Drugs

Terbinafine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Terbinafine	Squalene monooxygenase	Protein	Humans	No	Inhibitor	Details
Terbinafine	Squalene monooxygenase	Protein	Yeast	Yes	Inhibitor	Details