Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor potentiates the anticonvulsant activity of tiagabine against pentylenetetrazol-induced convulsions in mice.
Numerous studies have implicated prostaglandins as potential modulators in seizure activity. The objective of the present study was to elucidate the effect of rofecoxib (selective COX-2 inhibitor) alone or in combination with newer antiepileptic drug tiagabine (gamma-amino acid reuptake inhibitor) against pentylenetetrazol (PTZ) (80 mg/kg, i.p.)-induced chemoconvulsions in mice. Rofecoxib or tiagabine was administered 45 min prior to the PTZ challenge. In combination study, rofecoxib was administered 10 min before tiagabine and after 35 min the animals were challenged with convulsive dose of PTZ. Mean onset time of jerks, clonus and extensor phases following PTZ challenge was noted. Pretreatment with rofecoxib (1-5.0 mg/kg, i.p.) or tiagabine (1-10 mg/kg, i.p.) dose dependently protected the animals against PTZ-induced convulsions. The mean onset time of jerks, clonus and extensor phase were increased. A subeffective dose of rofecoxib (0.5 mg/kg, i.p.) potentiated the effect of subprotective dose of tiagabine (0.5 mg/kg, i.p.). The results of the present study suggested that the protective effect of rofecoxib, a COX-2 inhibitor against PTZ-induced convulsions may be possibly through the GABAergic modulation. Rofecoxib may have a place as adjuvant therapy with standard antiepileptic drugs such as tiagabine in the treatment of epilepsy.
Dhir
A
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.
Kulkarni
S K
SK
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007783:Lactones / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D010433:Pentylenetetrazole; D012640:Seizures / Q000188:drug therapy*; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use*; D000078308:Tiagabine
D000927:Anticonvulsants; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D009557:Nipecotic Acids; D013450:Sulfones; C116926:rofecoxib; D010433:Pentylenetetrazole; D000078308:Tiagabine