Abdul-Ghani A S, Attwell P J, Bradford H F
Department of Biology and Biochemistry, Birzeit University, West-Bank, Israel.
Eur J Pharmacol. 1997 May 12;326(1):7-14. doi: 10.1016/s0014-2999(97)00139-8.
The influence of 2-chloroadenosine, a non-metabolizable adenosine A1 receptor agonist, was tested on the development of electrically kindled amygdala and on the seizure responses of fully kindled rats. Focal intra-amygdaloid injection of 2-chloroadenosine (1-10 nmol/0.5 microl) 20 min before applying the daily kindling stimulus prevented the development of the kindling process. The behavioural seizure score and the afterdischarge duration were reduced below their initial values. The antiepileptogenic effects of 1 and 10 nmol of 2-chloroadenosine were reversible 8-10 days after withdrawal of the drug. When 2-chloroadenosine was tested on fully developed stage 5 amygdala-kindled seizures, it increased the generalised seizure threshold in a dose-dependent manner. A maximum efficiency of 125% (P < 0.001) was achieved with 5 nmol and the median effective dose was 0.55 nmol. Higher doses resulted in the reduced anticonvulsant effect (P < 0.05). With the same daily stimulation, 2-chloroadenosine 5 nmol in 0.5 microl vehicle, significantly reduced the maximum seizure score by 90%, the afterdischarge duration by 88% and completely blocked the generalised seizure duration. The antiseizure activity of the drug lasted for 3 days. In conclusion, 2-chloroadenosine not only acts as an anticonvulsant against electrically induced kindled seizures as described here, and against audiogenic seizures, electroshock and a variety of chemical convulsants as described by others, it prevents the development of the epileptic state by kindling-stimulation, i.e., it is antiepileptogenic. We theorise here that this is due to its blockade of presynaptic glutamate release.
测试了不可代谢的腺苷A1受体激动剂2 - 氯腺苷对电点燃杏仁核发育以及对完全点燃大鼠癫痫发作反应的影响。在每日施加点燃刺激前20分钟，向杏仁核内局部注射2 - 氯腺苷（1 - 10纳摩尔/0.5微升）可阻止点燃过程的发展。行为性癫痫发作评分和放电后持续时间降至初始值以下。停药8 - 10天后，1纳摩尔和10纳摩尔2 - 氯腺苷的抗癫痫发生作用是可逆的。当在完全发育的5期杏仁核点燃癫痫发作时测试2 - 氯腺苷，它以剂量依赖方式提高全身性癫痫发作阈值。5纳摩尔时达到最大效率125%（P < 0.001），半数有效剂量为0.55纳摩尔。更高剂量导致抗惊厥作用减弱（P < 0.05）。在相同的每日刺激下，0.5微升溶媒中5纳摩尔的2 - 氯腺苷显著使最大癫痫发作评分降低90%，放电后持续时间降低88%，并完全阻断全身性癫痫发作持续时间。该药物的抗癫痫发作活性持续3天。总之，2 - 氯腺苷不仅如本文所述对电诱导的点燃癫痫发作以及如其他人所述对听源性癫痫发作、电休克和多种化学惊厥剂具有抗惊厥作用，它还通过点燃刺激预防癫痫状态的发展，即它具有抗癫痫发生作用。我们在此推测这是由于其对突触前谷氨酸释放的阻断作用。
