Background: Ivabradine, Hyperpolarization activated cyclic nucleotide gated (HCN) channel blocker, is the most specific blocker of central nervous system Ih current. Valporate is one of the most commonly used antiepileptic drugs. Objectives: investigate the possible anticonvulsant effect of Ivabradine and its interaction with valporate in pentylenetetrazole (PTZ) induced-kindling in mice. Materials& Methods: mice were divided into four groups, "Group 1", "vehicletreated group" "Group 2", "PTZ kindling Control group "Group 3: Ivabradine ", group 4 Valproate (VPA) group 5" Ivabradine and VPA. Kindling was produced by repeated intraperitoneally (i.p). administration of PTZ (40mg/kg), every other day for 9 doses. Both drugs were administered i.p., 30 minutes before each PTZ injection. Seizure score, latency were recorded. Their brains were removed for assessment of oxidant/antioxidant status and anti-inflammatory cascades. Results: Ivabradine and VPA individually significantly decreased seizure score and co administration of both drugs significantly decreased seizure score less than either vaporate or Ivabradine. Both drugs significantly increased latency to seizures. Ivabradine, VPA and their combined administration significantly elevated brain level of GSH, catalase and significantly decreased levels of nitrite, MDA, IL1β, and TNFα as compared to PTZ control group. Co-administration of both drugs resulted in a significant elevation in the brain level of GSH, catalase concomitant with a significant reduction in the brain levels of MDA, IL1β and TNFα as compared to either VPA or ivabradine groups. Conclusion: Ivabradine has anticonvulsant effect and potentiates the effect of VPA which may be attributes to HCN channel blockade, antioxidant and anti-inflammatory effects.

Background: Pain is an unpleasant sensation experienced when tissues are damaged. Therapeutic management of pain requires consideration of many factors due multiplicity of etiopathogenesis. Objectives: The present study was designed to assess and compare the analgesic effects of gabapentin, diclofenac and tizanidine as well as their combinations in acute and chronic pain. Methods: 128 rats were randomly allocated into two main equal categories; one for acute inflammatory and other for chronic neuropathic pain study. The acute category was divided into 8 equal groups; control, carrageenan, diclofenac, gabapentin, tizanidine, gabapentin-diclofenac, gabapentintizanidine and tizanidine-diclofenac groups. Acute inflammatory pain was induced by carrageenan injection in the animals paw. In the chronic category neuropathic pain was induced by right sciatic nerve ligation except for control and sham groups. This category was divided into; control, sham, gabapentin, tizanidine, gabapentin-diclofenac, gabapentin-tizanidine and tizanidinediclofenac groups. The mean reaction time was assessed in all groups. Results: In acute pain the three drugs and their combinations had significant analgesic effects. Tizanidine potentiated the analgesic effects of diclofenac and gabapentin. In chronic neuropathic pain diclofenac and gabapentin had significant analgesic action while, tizanidine had no analgesic effect. Conclusion: Tizanidine didn't show analgesic effect on chronic pain but potentiated the analgesic effect of gabapentin and diclofenac in acute pain model.