Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice.
Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants viz. lamotrigine (5mg/kg, p.o.), oxcarbazepine (15mg/kg, p.o.) and topiramate (10mg/kg, p.o.) on cognitive function and oxidative stress during pentylenetetrazole (PTZ)-kindling in mice. Kindling was induced by the administration of PTZ (25mg/kg, i.p.) on every alternate day till 5 weeks. Cognition was assessed after the development of kindling. Elevated plus maze (EPM) and passive avoidance response (PAR) tests were carried out after 24h and 48h of the last PTZ administration. After completion of behavioural tests malondialdehyde (MDA), glutathione levels, superoxide dismutase and catalase activity were measured as an indicator of oxidative stress. The results of the present study indicate that topiramate (10mg/kg) administration to kindled animals increased transfer latency and decreased step-down latency in EPM and PAR tests, respectively. However, lamotrigine and oxcarbazepine did not alter the two parameters. Topiramate administration to kindled as well as non-kindled animals has shown increase in MDA and decrease in glutathione levels. Lamotrigine and oxcarbazepine did not show significant alteration in oxidative stress parameters. To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer.
Department of Pharmacology, University College of Medical Sciences (University of Delhi) & GTB Hospital, New Delhi 110095, India. nidhi.bharal@gmail.com
Nidhi Bharal
NB
Agarwal
Nitin Kumar
NK
Agarwal
Pramod Kumari
PK
Mediratta
Krishna Kishore
KK
Sharma
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004924:Escape Reaction / Q000187:drug effects; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D000077213:Lamotrigine; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D000078330:Oxcarbazepine; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000009:adverse effects*; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy; D013482:Superoxide Dismutase / Q000378:metabolism; D000077236:Topiramate; D014227:Triazines / Q000494:pharmacology
D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D010433:Pentylenetetrazole