首页   按字顺浏览 期刊浏览 卷期浏览 Selective action of allylamines and its therapeutic implications
Selective action of allylamines and its therapeutic implications

 

作者: RyderNS,  

 

期刊: Journal of Dermatological Treatment  (Taylor Available online 1992)
卷期: Volume 3, issue sup1  

页码: 3-7

 

ISSN:0954-6634

 

年代: 1992

 

DOI:10.3109/09546639209088693

 

出版商: Taylor&Francis

 

数据来源: Taylor

 

摘要:

Terbinafine (Lamisil®) is an orally active antimycotic of the allylamine class with activity against a wide range of pathogenic fungi, especially dermatophytes. The primary mechanism of action of these compounds is the specific inhibition of fungal squalene epoxidase. Measurement of ergosterol biosynthesis by incorporation of radiola-belled precursors indicates a correlation between inhibition of growth and of ergosterol biosynthesis in a range of pathogenic fungi. Fungi treated with these drugs accumulate squalene while becoming deficient in ergosterol, an essential component of fungal cell membranes. The characteristic primary fungicidal action of terbinafine and related allylamines is closely associated with the development of high intracellular squalene concentrations, which are thought to interfere with fungal membrane function and cell wall synthesis. Terbinafhe is a potent non-competitive inhibitor of the microsomal squalene epoxidase from Candida (Ki= 30 nM). In contrast, inhibition of rat liver squalene epoxidase only occurs at very high drug concentrations (Ki= 77μM) and is also qualitatively different, being competitive with squalene. Terbinafine thus has no effect on cholesterol biosynthesisin vivo. Squalene epoxidase is not an enzyme of the cytochrome P-450 type and, therefore, the allylamines have no intrinsic potential for inhibition of this class of enzymes.

 

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