Title:Activation of Adenosine Receptor Potentiates the Anticonvulsant Effect of Phenytoin Against Amygdala Kindled Seizures
VOLUME: 14 ISSUE: 3
Author(s):Zhen Sun, Xiao-Ling Zhong, Yu Zong, Zhong-Chen Wu, Qun Zhang, Jin-Tai Yu and Lan Tan
Affiliation:Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao 266071, PR China.
Keywords:Adenosine, agonist, amygdala-kindled, blood-brain barrier, epilepsy, phenytoin.
Abstract:Drug resistance in epilepsy is considered as a complicated and multifactorial problem. Poor
penetration of antiepileptic drugs (AEDs) across blood-brain barrier (BBB) into the brain, which
results in insufficient level of the drugs at the targeted brain region, has been discussed as one
mechanism contributing to pharmacoresistance of epilepsies. Therefore, modulating permeability of BBB is the effective
treatment strategy since it facilitates the entry of AEDs into the central nervous system (CNS). Recently, signaling
through receptors for the adenosine has been identified as a potent modulator of BBB permeability. This paper aimed to
investigate the effects of auxiliary application of adenosine receptor (AR) agonist on amygdala-kindled seizures in adult
male Wistar rats. When fully kindled seizures were achieved by daily electrical stimulation of the amygdala, rats were
randomly divided into three groups: control, phenytoin, and phenytoin (PHT) + 5'-N-ethylcarboxamidoadenosine (NECA)
groups. NECA (0.08mg/kg, i.v.) was applied to the PHT+NECA group after the administration of PHT (75mg/kg, i.p. on
the first day; 50mg/kg, i.p. on the following 9 days). Intravenous infusion of NECA resulted in a significant increase in
brain PHT levels as compared with the PHT treatment alone. On the other hand, the auxiliary application of NECA
dramatically decreased the frequency of generalized seizures and seizure stage, shortened duration of afterdischarge and
generalized seizures, as well as the elevated the afterdischarge threshold and generalized seizures threshold. Our study
demonstrated that auxiliary application of AR agonist enhanced brain antiepileptic drug levels and strengthened the
anticonvulsant properties of PHT against amygdala kindled seizures.
