Evaluation of antiepileptic activity of aspirin in combination with newer antiepileptic lamotrigine in mice.
Neurotransmitters such as GABA, glutamate and prostaglandins mediate synaptic transmission and their modulation may play a role in the generation of seizures. Numerous studies implicate prostaglandins as potential modulators of seizure activity. This study was designed to assess the antiepileptic activity of aspirin and to investigate the potentiation of its activity in combination with a subconvulsive dose of lamotrigine. Graded doses of aspirin and lamotrigine were used in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure models in mice. To study the interaction of aspirin and lamotrigine, ED(25) doses of aspirin (250 mg/kg) and lamotrigine (1.5 mg/kg) were used in the two seizure models. Aspirin dose-dependently decreased the incidence of seizures in the PTZ-model mice but did not show any effect in MES-model mice. ED(25) doses of aspirin and lamotrigine showed 100% protection of the PTZ seizure model. Aspirin alone in doses of 400 and 800 mg/kg and in combination decreased mortality in the PTZ model. Aspirin showed a significant anticonvulsant effect in PTZ seizure mode. Potentiation of the anticonvulsant effect of lamotrigine with aspirin was shown in the PTZ model, indicating that prostaglandins could play an important role in this seizure model.
Tandon
M
M
Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh-160012, India.
Anuradha
K
K
Pandhi
P
P
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004357:Drug Synergism; D004597:Electroshock / Q000379:methods; D007274:Injections, Intraperitoneal; D000077213:Lamotrigine; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D014227:Triazines
D000927:Anticonvulsants; D004338:Drug Combinations; D014227:Triazines; D001241:Aspirin; D000077213:Lamotrigine; D010433:Pentylenetetrazole