CHA (2 mg/kg, i.p.) and
CPPene (2.5 mg/kg, i.p.) were found to enhance the
anticonvulsant activity of the tested
antiepileptic drugs against both electro convulsions and PTZ-induced convulsions. Both CHA and
CPPene significantly decreased the ED50 values of these drugs against both electro convulsions and PTZ-induced convulsions, and increased the convulsive threshold. CHA (2 mg/kg, i.p.) and
CPPene (2.5 mg/kg, i.p.) did not affect the plasma level of any of the tested
antiepileptic drugs, indicating no pharmacokinetic interactions at the systemic administration. CHA (2 mg/kg, i.p.) or
CPPene (2.5 mg/kg, i.p.), alone or in combination with the tested
antiepileptic drugs produced no significant changes in their effects on the heart rate, blood pressure, body temperature, gross behavior or on the locomotor activity of experimental animals. Combinations of the
antiepileptic drugs with CHA (2 mg/kg, i.p.) or
CPPene (2.5 mg/kg, i.p.) were also devoid of significant effects on the motor performance and long-term memory in mice demonstrated by the Chimney test and passive avoidance task. CHA (5 mg/kg, i.p.) alone or in combination with the tested
antiepileptic drugs produced inhibition of locomotor activity and motor coordination, sedation and
hypothermia as well as impairing of long-term memory.
CONCLUSION:
Adenosine A1 agonists and
NMDA antagonists enhance the efficacy of common
antiepileptic drugs, indicating the involvement of
adenosine and
NMDA receptors in the convulsive pathway. The potential therapeutic benefits of such interactions may be taken into consideration and merit further investigations in animals and humans.