Deshpande Laxmikant S, DeLorenzo Robert J
Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA.
Neuroreport. 2011 Jan 5;22(1):15-8. doi: 10.1097/WNR.0b013e3283413231.
Status epilepticus (SE) is a major neurological disorder and SE survivors often develop acquired epilepsy and cognitive deficits. Thus, it is important to stop SE and limit brain damage. However, rapid pharmacoresistance develops to anticonvulsants as seizure duration lengthens. Recently, acetaminophen was reported to increase endocannabinoid levels by its conversion to AM 404. Further, cannabinoids are potent anticonvulsants. Here we investigated whether acetaminophen would block SE-like activity in hippocampal neurons. Exposure of cultured hippocampal neurons to a low Mg2+ medium elicits high-frequency epileptiform discharges that exceed 3 Hz (in-vitro SE). Acetaminophen (500 μM) blocks the SE-like activity. CB1 receptor antagonist SR 141716A (1 μM) blocked this inhibitory effect of acetaminophen on SE, indicating that acetaminophen was mediating its anticonvulsant effects through CB1 receptors.
癫痫持续状态（SE）是一种主要的神经系统疾病，SE幸存者常发展为获得性癫痫和认知缺陷。因此，停止SE并限制脑损伤很重要。然而，随着癫痫发作持续时间延长，抗惊厥药物会迅速产生耐药性。最近，据报道对乙酰氨基酚通过转化为AM 404来增加内源性大麻素水平。此外，大麻素是强效抗惊厥药。在此，我们研究了对乙酰氨基酚是否会阻断海马神经元中的SE样活动。将培养的海马神经元暴露于低镁培养基会引发超过3 Hz的高频癫痫样放电（体外SE）。对乙酰氨基酚（500 μM）可阻断SE样活动。CB1受体拮抗剂SR 141716A（1 μM）可阻断对乙酰氨基酚对SE的这种抑制作用，表明对乙酰氨基酚是通过CB1受体介导其抗惊厥作用的。
