Reduced Estradiol Synthesis by Letrozole, an Aromatase Inhibitor, Is Protective Against Development of Pentylenetetrazole-Induced Kindling in Mice

The study investigated the effects of letrozole, an aromatase inhibitor, on pentylenetetrazole (PTZ)-induced kindling in Swiss albino mice. Letrozole, administered at 1 mg/kg, significantly reduced the incidence of kindling, delayed seizure onset, and decreased seizure severity by lowering plasma levels of the pro-convulsant hormone 17β-estradiol. The study also explored the role of finasteride, a 5α-reductase inhibitor, but found it did not affect PTZ-kindling or alter letrozole's protective effects. The findings suggested that aromatase inhibitors like letrozole could be potential antiepileptic agents by reducing pro-convulsant neurosteroids and redirecting synthesis towards anticonvulsant neurosteroids.