Apland J P, Braitman D J
Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Brain Res. 1990 Oct 8;529(1-2):277-85. doi: 10.1016/0006-8993(90)90838-3.
Three commonly used antitussive compounds were tested for their ability to block epileptiform activity recorded extracellularly from hippocampal and olfactory cortex slices maintained in vitro. Antitussives were bath-applied to brain slices either before or after epileptiform activity was induced. Dextromethorphan (DM) prevented electrically evoked epileptiform afterdischarges and arrested spontaneous bursting induced by exposure to added NMDA or to Mg2(+)-free medium. In contrast, caramiphen (CM) and carbetapentane (CB) were effective against epileptiform activity induced by Mg2(+)-free medium, but not by NMDA. Atropine was not effective in blocking epileptiform activity at concentrations 10 times the effective concentration of CM, which has known cholinolytic activity. Our results suggest that all these antitussives exert their anticonvulsant action at the DM binding site. Neither cholinolytic activity nor antagonism of the NMDA receptor-channel complex appears to be necessary for antitussives to prevent or arrest epileptiform activity. DM appears to have a separate NMDA-antagonist property in addition to its actions at the DM site. Our neurophysiological evidence supports the hypothesis that these antitussives have anticonvulsant properties independent of any action at the NMDA receptor-channel complex.
对三种常用的镇咳化合物进行了测试，以检验它们阻断从体外培养的海马体和嗅皮质切片细胞外记录的癫痫样活动的能力。在诱导癫痫样活动之前或之后，将镇咳药浴用于脑切片。右美沙芬（DM）可预防电诱发的癫痫样后放电，并抑制因暴露于添加的NMDA或无镁（Mg2+）培养基而诱发的自发性爆发。相比之下，卡拉美芬（CM）和卡比沙明（CB）对无镁（Mg2+）培养基诱发的癫痫样活动有效，但对NMDA诱发的无效。阿托品在浓度为具有已知胆碱能溶解活性的CM有效浓度10倍时，对阻断癫痫样活动无效。我们的结果表明，所有这些镇咳药在DM结合位点发挥其抗惊厥作用。镇咳药预防或抑制癫痫样活动似乎既不需要胆碱能溶解活性，也不需要对NMDA受体通道复合物的拮抗作用。除了在DM位点的作用外，DM似乎还具有单独的NMDA拮抗剂特性。我们的神经生理学证据支持这样的假设，即这些镇咳药具有独立于在NMDA受体通道复合物上的任何作用的抗惊厥特性。
