Anticonvulsant effects of bretazenil (Ro 16-6028) during ontogenesis.
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.
Kubová
H
H
Institute of Physiology, Czechoslovak Academy of Sciences, Prague.
Rathouská
J
J
Mares
P
P
D000328:Adult; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats / Q000254:growth & development*; D018079:Receptors, GABA / Q000187:drug effects*
D001570:Benzodiazepinones; D018079:Receptors, GABA; C054626:bretazenil; D010433:Pentylenetetrazole