Effects of ketoconazole on oestrus cycle and convulsant action of pentylenetetrazol in mice.
The frequency of oestrus cycles in female mice was significantly reduced by the implantation of a pellet of subcutaneous ketoconazole (50 mg every 6 days). The effect was more pronounced after 22 days than after 13 days and it was probably related with the progressive reduction in steroid synthesis induced by the inhibition of key steroidogenic P450 cytochromes by the drug. In addition, the influence of ketoconazole on the incidence of seizures after the administration of intraperitoneal pentylenetetrazol was evaluated in female mice. Pentylenetetrazol produced a higher percentage of seizures during dioestrus than during oestrus. Pretreatment with ketoconazole significantly increased the percentage of animals with induced seizures in oestrus but not in dioestrus as compared to controls, probably through reduced progesterone levels. The reduced seizure threshold confirm the modulatory role exerted by progesterone on central nervous system excitability, and may be relevant in epileptic patients undergoing antifungal therapy.
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Faculty of Medical Sciences, Pharmacology Program, University of Santiago de Chile, Alameda 3363, P.O. Box 442, Correo 2, Santiago, Chile. gpinardi@machi.med.uchile.cl
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Bustamante
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Pinardi
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D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects*; D005260:Female; D007279:Injections, Subcutaneous; D007654:Ketoconazole / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors
D000935:Antifungal Agents; D003292:Convulsants; D007654:Ketoconazole; D010433:Pentylenetetrazole