Swartzwelder H S, Bragdon A C, Sutch C P, Ault B, Wilson W A
J Pharmacol Exp Ther. 1986 Jun;237(3):881-7.
Baclofen is used clinically to treat spasticity, but has received little attention as a potential antiepileptic agent. To explore the antiepileptic potential of baclofen further, we tested its effect on stimulus train-induced bursting, an in vitro model of hippocampal epileptiform activity. In hippocampal slices prepared from male rats, extracellular field potentials were recorded in stratum pyramidale of CA3, and electrical stimuli were delivered to s. radiatum of CA3. After stable responses to single stimuli were established, stimulus trains were delivered every 5 min until stable triggered and spontaneous population bursting were elicited. (+/-)-Baclofen was bath-applied to the slices at varying concentrations to study its ability to suppress synaptic transmission and epileptiform activity. EC50 values for suppression of orthodromic population spike amplitude, of triggered burst duration and of spontaneous burst frequency were 2300, 355 and 26.9 nM, respectively; all statistically significantly different. These findings suggest that baclofen suppresses epileptiform electrical activity in the hippocampus at concentrations well below those which suppress normal synaptic transmission, and support renewed consideration of baclofen as an antiepileptic agent.
巴氯芬在临床上用于治疗痉挛，但作为一种潜在的抗癫痫药物却很少受到关注。为了进一步探索巴氯芬的抗癫痫潜力，我们测试了其对刺激串诱导的爆发性放电的影响，这是一种海马癫痫样活动的体外模型。在从雄性大鼠制备的海马切片中，在CA3区锥体层记录细胞外场电位，并将电刺激施加到CA3区辐射层。在对单个刺激建立稳定反应后，每5分钟施加一次刺激串，直到引发稳定的触发和自发群体爆发性放电。以不同浓度将（±）-巴氯芬浴应用于切片，以研究其抑制突触传递和癫痫样活动的能力。抑制顺向群体峰电位幅度、触发爆发持续时间和自发爆发频率的半数有效浓度（EC50）分别为2300、355和26.9 nM；均具有统计学显著差异。这些发现表明，巴氯芬在远低于抑制正常突触传递的浓度下就能抑制海马中的癫痫样电活动，并支持重新考虑将巴氯芬作为一种抗癫痫药物。
