Additive effects of antiepileptic drugs and pentylenetetrazole on hearing

The long-term effect of three of the most widely used antiepileptic drugs at relevant doses on the hearing decline that accompanies pentylenetetrazole (PTZ)-induced experimental epilepsy was investigated here, and compared with the effect of vinpocetine (VPC), which is a drug with antiepileptic potential. For this purpose, cortical activity (monitored by the EEG) and auditory sensitivity, as indicated by brainstem. auditory evoked potential (BAEP) threshold at 4 and 8 kHz tone frequencies, were determined in guinea pigs daily injected for 28 days with vehicle (control), 20 mg/kg carbamazepine (CBZ), 6 mg/kg phenytoin (PHT), 30 mg/kg valproate (VPA) or 2 mg/kg vinpocetine (VPC) before and after the administration of PTZ at a convulsing dose (100 mg/kg). Results show that all the antiepileptic drugs tested were more or less effective in preventing PTZ-induced seizures. The long-term treatment with VPC decreased the auditory threshold, whereas the long-term treatment with CBZ, PHT or VPA increased the auditory threshold to a similar extent as the convulsing agent, PTZ. The combined effects of the antiepileptic drugs and PTZ on auditory threshold were additive. Therefore, only VPC prevented the increase in the auditory threshold induced by PTZ. It is concluded that the hearing loss produced by the long-term treatment with the most commonly used antiepileptic drugs could be aggravated by the illness. The prevention exerted by VPC on the hearing decline that accompanies experimental epilepsy, along with its capacity to control seizures at low doses in this and other animal models of epilepsy, would make VPC a valid candidate for the treatment of epilepsy. (c) 2006 Elsevier Ireland Ltd. All rights reserved.