Epilepsy is a big problem facing the society. There are a different modalities of treatment of epilepsy that extend for a long period. Pregabalin is classified as a miscellaneous analgesic and anticonvulsant and is structurally related to gabapentin. Most of antiepileptic drugs can reduce neuronal hyperexcitability by inhibiting ion channels including Ca channels. The current study aimed to evaluate the role of nifedpine in combination with pregabaline and gabapentin in pentylenetetrazole (PTZ)-kindled mice. Sixty mice were divided into 6 main groups (n=10), Positive control group treated by sub-convulsive dose of PTZ (35 mg/kg, i.p.), nifedipine treated group (20 mg/kg), Pregabaline treated group (40 mg/kg i.p.), Gabepentin treated group (200 mg/kg i.p.), Nifedipine + pregabaline group, Nifedipine+ gabapentin group. Pain tolerance measurement using right paw pad pressure tolerance was done. Our data indicate that gabapentin, pregabaline and nefidipine significantly decrease seizure activity in comparison to PTZ control mice (p<0.05) and these effects increase more significantly with combination of these drugs (p<0.009, p<0.011). In addition, gabapentin, pregabaline and nifedipine increase significantly pain tolerance in relation PTZ control mice (p<0.05) and coimplementation of both drugs either gabapentin with nifedpine or pregabaline with nifedipine show more synergistic significant effects on pain tolerance (p<0.001). In conclusion coapplication of these drugs together may lead to decrease of side effects and more control of epilepsy.