Effect of lamotrigine, levetiracetam & topiramate on neurobehavioural parameters & oxidative stress in comparison with valproate in rats.
OBJECTIVE
Though newer antiepileptic drugs are considered safer than conventional antiepileptics, the effects of lamotrigine, levetiracetam and topiramate on neurobehavioural functions are yet to be established. This study evaluated neurobehavioural parameters and oxidative stress markers in brain tissue of rats treated with lamotrigine, levetiracetam and topiramate compared to sodium valproate .


METHODS
Five groups of male Wistar rats were treated respectively with normal saline (control), sodium valproate (370 mg/kg), lamotrigine (50 mg/kg), levetiracetam (310 mg/kg) and topiramate (100 mg/kg) for 45 days. Neurobehavioural parameters were assessed using elevated plus maze (EPM), actophotometer, rotarod, passive avoidance and Morris water maze (MWM) at baseline and at the end of treatment. Oxidative stress parameters [malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD)] were estimated in rat brain at the end of treatment.


RESULTS
Valproate and lamotrigine showed no significant effect on learning and memory in passive avoidance and MWM tests. However, levetiracetam and topiramate reduced retention memory significantly as compared to control (P<0.01) and lamotrigine (P<0.05) groups. Performances on EPM, rotarod and actophotometer were not significantly different between the groups. In comparison to control group, MDA was higher in the levetiracetam and topiramate (360.9 and 345.9 nmol/g of homogenized brain tissue, respectively) groups. GSH and SOD activity were significantly reduced by valproate and levetiracetam treatment. Lamotrigine did not induce significant oxidative stress.


CONCLUSIONS
Long-term and therapeutic dose treatment with levetiracetam and topiramate significantly impaired learning and memory, which was not seen with valproate and lamotrigine in rats. Levetiracetam, topiramate and valproate augmented oxidative stress, whereas lamotrigine has little effect on it. These antiepileptic drugs are used in clinical practice, hence pharmaco- vigilance studies are required to evaluate their safety profile.
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Sudhir Chandra
SC
Sarangi
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi; Department of Pharmacology, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India.
Ashish Kumar
AK
Kakkar
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Ritesh
R
Kumar
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Yogendra Kumar
YK
Gupta
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives; D005978:Glutathione / Q000378:metabolism; D000077213:Lamotrigine; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D000077287:Levetiracetam; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D000077236:Topiramate; D014227:Triazines / Q000008:administration & dosage; D014635:Valproic Acid / Q000008:administration & dosage
D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D000077287:Levetiracetam; D008315:Malondialdehyde; D014635:Valproic Acid; D013482:Superoxide Dismutase; D005978:Glutathione; D000077213:Lamotrigine; D010889:Piracetam