Anticonvulsant Effects of Bretazenil (Ro 16‐6028) During Ontogenesis

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Abstract
Anticonvulsant action of a new benzodiaze-pine, 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.