Kubová H, Rathouská J, Mares P
Institute of Physiology, Czechoslovak Academy of Sciences, Prague.
Epilepsia. 1993 Nov-Dec;34(6):1130-4. doi: 10.1111/j.1528-1157.1993.tb02145.x.
Anticonvulsant action of a new benzodiazepine, bretazenil (Ro 16-6028), was studied in 240 rats in five age groups: age 7, 12, 18, 25 and 90 days. Motor seizures induced by metrazol (pentamethylenetetrazol, PTZ, 100 mg/kg subcutaneously (s.c.) except for 18-day-old rats which received a dose of 90 mg/kg) served as a model. Animals were pretreated with Ro 16-6028 in doses of 0.001-0.1 mg/kg intraperitoneally (i.p.) 10 min before metrazol. Both types of metrazol-induced seizures, minimal (mMS, predominantly clonic with preserved righting ability) and major (MMS, generalized tonic-clonic), were suppressed by Ro 16-6028 in a dose-dependent manner. Major seizures were always more sensitive to Ro 16-6028 than were minimal seizures. The youngest rats exhibited maximal effects of Ro 16-6028 against major seizures. On the other hand, this drug increased the incidence of minimal seizures in 7- and 12-day-old rats, i.e., in age groups in which this type of seizure is rare under control conditions.
在五个年龄组（7日龄、12日龄、18日龄、25日龄和90日龄）的240只大鼠中研究了一种新型苯二氮䓬类药物布瑞西坦（Ro 16-6028）的抗惊厥作用。以美解眠（戊四氮，PTZ，除18日龄大鼠接受90mg/kg剂量外，其余皮下注射100mg/kg）诱发的运动性癫痫作为模型。在注射美解眠前10分钟，给动物腹腔注射0.001-0.1mg/kg剂量的Ro 16-6028。Ro 16-6028以剂量依赖性方式抑制了两种类型的美解眠诱发的癫痫发作，即轻微发作（mMS，主要为阵挛性发作且保留翻正能力）和严重发作（MMS，全身性强直阵挛性发作）。严重发作对Ro 16-6028总是比轻微发作更敏感。最年幼的大鼠对Ro 16-6028抗严重发作表现出最大效果。另一方面，该药物增加了7日龄和12日龄大鼠轻微发作的发生率，即在对照条件下这种类型发作罕见的年龄组中。
