Abstract

EFFECT OF AMITRIPTYLINE ON ANTICONVULSANT ACTIVITIES OF DIVALPROEX SODIUM ON MES AND PTZ INDUCED SEIZURES IN RATS

Tamrakar AK*, Nagalakshmi NC, Swamy SK, Janadri S, Shah M, Shahu G

ABSTRACT

The objective of this study was to investigate the type of interactions between Amitriptyline (AMI) and Divalproex (DVPX) against different animal model. Divalproex alone and in combination with AMI were examined in the rat model of maximal electroshock (MES test) and Pentylenetetrazoe (PTZ) induced convulsion. Combination of AMI and DVPX were significantly supraadditive (synergistic) in MES test and PTZ induced convulsion. AMI significantly decreased the duration of hind limb tonic extension (HLTE). The percentage prolongation of onset of clonic convulsion was enhanced to 86.76% in combination treatment. VPA pretreatment can block the N-methyl-Daspartate (NMDA) receptor. The effect of VPA is synergistically potentiated by AMI, which acts as NMDA receptor antagonist. Increase in extracellular 5-HT level inhibits many types of seizure. AMI has significant role in increase in brain 5-HT concentration. GABAB receptors are able to affect the development of the epileptic kindling state induced by pentylenetgetrazole. VPA and AMI both affect GABAergic neurotransmission by acting on GABA receptors, enhancing responses of GABAB receptor. Synergistic interaction was found between the two interacting drugs. The combination of AMI and DVPX can be advantageous in epilepsy, and therefore should be recommended for further study in clinical conditions.

Keywords: Divalproex, Amitriptyline, Antiepileptic drugs, Electroshock seizure test, Pentylenetetrazole induced convulsion.