Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice

Metab Brain Dis. 2017 Aug;32(4):1051-1060. doi: 10.1007/s11011-017-9979-2. Epub 2017 Mar 9.


Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

Keywords: Amlodipine; Antiepileptic drugs; Diazepam; Pentylenetetrazole; Pregabalin; Valproate.

MeSH terms

  • Amlodipine / therapeutic use*
  • Animals
  • Anticonvulsants / therapeutic use*
  • Disease Models, Animal
  • Drug Synergism
  • Drug Therapy, Combination
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy*
  • Male
  • Mice
  • Pentylenetetrazole
  • Pregabalin / therapeutic use*
  • Seizures / chemically induced
  • Seizures / drug therapy*


  • Anticonvulsants
  • Amlodipine
  • Pregabalin
  • Pentylenetetrazole