Toxicological and pharmacological properties of fenticonazole, a new topical antimycotic.
The acute oral and subchronic (6 weeks) topical toxicity of alpha-(2,4-dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476) was studied in mice, rats, guinea pigs and beagle dogs. The acute oral LD50 in mice and rats was found to be 3000 mg/kg, while the i.p. acute toxicity was 1191 mg/kg in mice and between 309 and 440 mg/kg in rats. The acute oral LD50 in beagle dogs was 1000 mg/kg. Percutaneous subchronic (6 weeks) toxicity was evaluated in guinea pigs and beagle dogs. Both species of animals exhibited no toxic effect attributable to the treatment with fenticonazole and no histopathologic changes were attributed to the drug treatment. Fenticonazole did not affect numerous pharmacological and physiological parameters (blood pressure, heart rate, pulmonary ventilation, nor did it interfere with the activity of histamine, adrenaline, noradrenaline and acetylcholine). It does not possess analgesic or antiinflammatory activity at high doses (100 mg/kg p.o.). In mice it exhibits a slight CNS depressant activity, milder than that of miconazole.
D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents; D002490:Central Nervous System / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004285:Dogs; D004906:Erythrocyte Count; D005260:Female; D006168:Guinea Pigs; D006454:Hemoglobins; D007093:Imidazoles / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010276:Parasympatholytics; D051381:Rats
D000935:Antifungal Agents; D006454:Hemoglobins; D007093:Imidazoles; D010276:Parasympatholytics; D002784:Cholesterol; C033486:fenticonazole