Amlodipine enhances the activity of antiepileptic drugs against pentylenetetrazole-induced seizures

Amlodipine (AML), which belongs to the 1,4-dihydropyridin calcium channel a ntagonists, possesses pharmacological and pharmacokinetic profile that dist inguishes it from other agents of this class. Pentylenetetrazole (PTZ)-indu ced clonic and tonic convulsions in mice were significantly reduced by admi nistration of AML at 10 mg/kg. At this dose AML remained without influence upon the plasma level of PTZ. The ED50 value of AML against clonic seizures induced by PTZ was 5.4 mg/kg. This calcium channel antagonist (at 2.5 mg/k g) combined with ethosuximide (ETX), valproate magnesium (VPA) or phenobarb ital (PB) significantly reduced their ED50 values against clonic phase of P TZ-induced seizures. AML administered alone or in combination with antiepil eptic drugs (AEDs) worsened the motor performance of mice in the chimney te st. However, these treatments remained without significant influence on the retention time in the passive avoidance test. Plasma levels of antiepilept ics remained unchanged in the presence of AML. The results indicate that AM L does not seem a good candidate for a combination therapy in epileptic pat ients because of its adverse potential. (C) 2001 Elsevier Science Inc. All rights reserved.