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Pathway Description
Terbinafine Action Pathway
Homo sapiens
Drug Action Pathway
Terbinafine (commonly known as Lamisil or Silka cream) is a synthetic allylamine anti-fungal used mainly for athletes foot and other fungal skin infections. While Terbinafine is most commonly used against the fungus species Trichophyton rubrum and Trichophyton mentagrophytes, but the ergosterol biosynthesis pathway for these species has not been studies enough to know the enzymes used for sure. Candida albicans is a fungus that Terbinafine can be used against and the enzyme squalene monooxygenase, which is the enzyme inhibited by this drug, has been properly researched for Candida albicans where it hasn't for other fungus species. Terbinafine can also be used against other Trichophyton species; Microsporum canis; Epidermophyton floccosum,11; Tinea species; Candida albicans and Malassezia furfur if infections of the skin.
Terbinafine works by inhibiting squalene monooxygenase which is an essential enzyme of Ergosterol biosynthesis. Terbinafine is transported into the fungal cell vis diffusion. Squalene monooxygenase catalyzes the synthesis of (S)-2,3-epoxysqualene from squalene. Since it is inhibited, it cannot continue on to synthesize lanosterol which is essential in the synthesis of ergosterol. Without ergosterol in the cell membrane, the cell membrane sees increased permeability which allows intracellular components to leak out of the cell. Ergosterol is also essential in cell membrane integrity so without that, eventually the cell collapses and dies.. The fungal cell also cannot synthesize new cell membranes for new fungus cells if there is no ergosterol. The inhibition of squalene monooxygenase also causes a buildup of squalene which is toxic to the fungal cell.
References
Terbinafine Pathway References
Ryder NS: Terbinafine: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol. 1992 Feb;126 Suppl 39:2-7.
Hill S, Thomas R, Smith SG, Finlay AY: An investigation of the pharmacokinetics of topical terbinafine (Lamisil) 1% cream. Br J Dermatol. 1992 Oct;127(4):396-400. doi: 10.1111/j.1365-2133.1992.tb00461.x.
Jensen JC: Clinical pharmacokinetics of terbinafine (Lamisil). Clin Exp Dermatol. 1989 Mar;14(2):110-3. doi: 10.1111/j.1365-2230.1989.tb00904.x.
Darkes MJ, Scott LJ, Goa KL: Terbinafine: a review of its use in onychomycosis in adults. Am J Clin Dermatol. 2003;4(1):39-65.
Sander CS, Hipler UC, Wollina U, Elsner P: Inhibitory effect of terbinafine on reactive oxygen species (ROS) generation by Candida albicans. Mycoses. 2002 Jun;45(5-6):152-5.
Graziano Castaldi, "Process for the preparation of terbinafine." U.S. Patent US20020123651, issued September 05, 2002.
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
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