Effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and progression of amygdala kindling.

Abstract

The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of male adult Wistar rats. Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced. Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administration of the drug. In addition, the effect on kindling progression was evaluated through ZM241385 injection before daily stimulation. In all experiments, behavioral changes in the rats in response to ZM241385 were monitored closely. The results showed that, in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) decreased afterdischage duration (ADD), motor seizure duration (MSD), stage 5 duration (S5D) and seizure duration (SD), but only the effect on ADD was dose-dependent. The doses of 0.001-0.1 nmol/L had no influence on stage 4 latency (S4L) and seizure stage (SS). The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all seizure parameters. In contrast to the results in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures. We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled seizures, it had potent anti-convulsant profile and little adverse effects at the dosage of 0.001-0.1 nmol/L, suggesting that the agent is effective against the amygdala-kindled seizures.

• Authors: Xiang Li, Huicong Kang, Xiaoyan Liu, Zhiguang Liu, Kai Shu, Xu Chen, Suiqiang Zhu
• Journal: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 32 Issue 2 Pg. 257-264 (Apr 2012) ISSN: 1672-0733 [Print] China
• PMID: 22528231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A2 Receptor Antagonists
• Receptor, Adenosine A2A
• Triazines
• Triazoles
• ZM 241385

Topics

• Adenosine A2 Receptor Antagonists (administration & dosage)
• Amygdala (drug effects, physiopathology)
• Animals
• Dose-Response Relationship, Drug
• Male
• Rats
• Rats, Wistar
• Receptor, Adenosine A2A (metabolism)
• Seizures (drug therapy, physiopathology)
• Treatment Outcome
• Triazines (administration & dosage)
• Triazoles (administration & dosage)