A time course of the protective action of clonazepam against metrazol-induced seizures was studied in 612 rats aged 7, 12, 18, 25 and 90 days. Two doses of clonazepam (0.1 and/or 1 mg/kg) were used and metrazol (100 mg/kg in all but 18-day-old animals where 90 mg/kg were given) was administered s.c. from 30 min to 48 hr. Not all time intervals were examined in all age groups. Eight to 14 rats were used for each time interval, dose and age group. Both doses exhibited a clear-cut antimetrazol action at all developmental stages studied. The protective action lasted longest in the 2 youngest groups and shortened progressively with age. The lower dose of clonazepam always exhibited shorter duration of action than the 1 mg/kg dose. Both doses were more efficient against major than against minimal metrazol seizures in 18-day-old and older rats where minimal seizures could be reliably elicited by metrazol.

Faculty of Pharmacy Charles University Hradec Králové Czechoslovakia

Epilepsy Research in the Institute of Physiology of the Czech Academy of Sciences in Prague

Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABAA and GABAB Receptors

Neonatal Clonazepam Administration Induces Long-Lasting Changes in Glutamate Receptors

Consequences of early postnatal benzodiazepines exposure in rats. II. Social behavior

Convulsant action of a benzodiazepine receptor agonist/inverse agonist Ro 19-4603 in developing rats