Clotrimazole

Because of their limited, activity, small spectmm, and side effects, the older topical antimycotics have generally been surpassed by newer antimycotic chemotherapeutic agents. These newer antimycotics for topical use iaclude the imida2ole derivatives clotrimazole, miconazole, econazole, isoconazole, sulconazole, fenticonazole, oxiconazole, bifonazole, butoconazole, ziaoconazole, tioconazole, and the triazole derivative, terconazole (Table 2) (5—7). The iatroduction of the azole derivatives represents a milestone ia the treatment of mycoses. 

Clotrimazole. The imidazole derivative clotrimazole (6) was iatroducedia 1969. Clotrimazole [23593-75-1] or l-((9-chloro-a,a-diphenylbenzyl)imidazole is a water-iasoluble antimycotic for topical appHcation, with a broad-spectmm activity against mycoses of the skin and the vagiaa. 

Clotrimazole and other azole derivatives have a different mode of action than the polyenes, eg, amphotericin B. The latter biad to the ergosterol present ia the membranes of yeasts and fungi, but azole derivatives inhibit the cytochrome P-450 dependent biosynthesis of ergosterol (8—11). This inhibition not only results in a reduction of ergosterol, but also in an accumulation of C-14 methyl sterols. They disturb membrane permeabiUty, inhibit cell rephcation, and are basically responsible, in combination with the reduction of ergosterol levels, for the antifungal action. 

Miconazole. Miconazole nitrate [22832-87-7] (Fig. 2), the 1-phenethyl-imidazole derivative first described in 1969, interferes at low doses with the cytochrome P-450 dependent ergosterol biosynthesis in yeasts and fungi. The result is accumulation of C-14 methylated sterols on the one hand and reduction of the ergosterol levels in the membranes on the other hand (12). Analogous to clotrimazole, this leads to a disturbance in the membranes it results in inhibition of ceU repHcation, mycelium development (in C. albicans) and finally, ceU death. High concentrations of miconazole, which may be achieved with topical use, disturb the orientation of phosphoHpids in the membranes, which produces leaks (13). 

Intermediate-conductance (IKCa) Sickle cell anemia, Diarrhea, Clotrimazole, ICA-15451 ICA-17043... 

Potassium Competitive Acid Blockers The pregnane X receptor (PXR) is a promiscuous nuclear receptor, that has evolved to protect the body from toxic chemicals. It is activated by a wide variety of xenobiotics including several diugs like rifampicin, hyperforin ( the active ingredient of St. John s wort), clotrimazole and others. PXR heterodimerizes with the... 

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

Griseofulvin (Grisactin) exerts its effect by being deposited in keratin precursor cells, which are then gradually lost (due to the constant shedding of top skin cells), and replaced by new, noninfected cells. The mode of action of flucytosine (Ancobon) is not clearly understood. Clotrimazole (Lotrimin, Mycelex) binds with phospholipids in the fungal cell membrane,... 

C Hs 71-43-2) see Budipine Clotrimazole Fexofenadine hydrochloride Ibuprofen Phenylmercuric borate ... 

C3H4N2 288-32-4) see Bifonazole Butoconazole Clotrimazole Eprosartan Fenticonazole Isoconazole Ketoconazole Miconazole Neticonazole hydrochloride Omoconazole nitrate Oxiconazole Ozagrel 1/f-imidazole lithium salt (C,H3LiN2 55986-39-5) see Flutrimazole 2-imidazolidinone... 

The mechanism of the reaction has not been eiuddated. Presumably iodine eliminates the imidazole ring from N-substituted imidazole derivatives such as clotrimazole, and this then couples with diazotized sulfanilic acid to yield an azo dye. 

Note The reaction is very specific for N-substituted imidazole derivatives. In serum investigations the detection limit was 50 ng clotrimazole per milliliter serum. The reagent can be employed on silica gel, kieselguhr and Si 50000 layers. 

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