Miconazole is an azole antifungal used to treat fungal infections affecting the vagina, mouth and skin, including candidiasis. Miconazole has some activity against Gram-positive bacteria as well. It is known by the brand names Aloe Vesta Antifungal, Baza, Critic-aid Clear, Desenex, Fungoid, Inzo, Lagicam, Lotrimin AF, Micatin, Micro-guard, Monistat, Monistat 1 Day Ovule Combination Pack, Monistat 3 Day Ovule Combination Pack, Monistat 7 Combination Pack, Oravig, Rash Relief Antifungal, Remedy Antifungal, Tetterine, Tineacide Antifungal, Ting, Vagistat, Vagistat 3 Day Combination Pack, Vusion, or Zeasorb. It is widely used to treat mucosal yeast infections, including both oral and vaginal infections; although intravenous miconazole is no longer available, a wide variety of suppositories, creams, gels, and tablet-based products are available. The primary mechanism of action is through inhibition of the CYP450 14α-lanosterol demethylase enzyme.Lanosterol 14-alpha demethylase is the enzyme that catalyzes the synthesis of 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol from lanosterol. With this enzyme inhibited ergosterol synthesis cannot occur which causes a significant low concentration of ergosterol in the fungal cell. Ergosterol is essential in maintaining membrane integrity in fungi. Without ergosterol, the fungus cell cannot synthesize membranes thereby increasing fluidity and preventing growth of new cells, which in turn leads to cation, phosphate, and low molecular weight protein leakage.. This leads to cell lysis which causes it to collapse and die. Additionally, miconazole inhibits fungal peroxidase and catalase while not affecting NADH oxidase activity, leading to an accumulation of hydrogen peroxide, which further leads to cell toxicity and death. It also leads to an increased production of reactive oxygen species (ROS). Increased intracellular ROS leads to downstream pleiotropic effects and eventual apoptosis. Lastly, likely as a result of lanosterol demethylation inhibition, miconazole causes a rise in intracellular levels of farnesol. This molecule participates in quorum sensing in Candida, preventing the transition from yeast to mycelial forms and thereby the formation of biofilms, which are more resistant to antibiotics.

Miconazole Pathway References