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Anticonvulsant effects of bretazenil (Ro 16-6028) during ontogenesis.

Abstract
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.
AuthorsH Kubová, J Rathouská, P Mares
JournalEpilepsia (Epilepsia) 1993 Nov-Dec Vol. 34 Issue 6 Pg. 1130-4 ISSN: 0013-9580 [Print] United States
PMID8243368 (Publication Type: Journal Article)
Chemical References
  • Benzodiazepinones
  • Receptors, GABA
  • bretazenil
  • Pentylenetetrazole
Topics
  • Adult
  • Animals
  • Benzodiazepinones (pharmacology)
  • Child
  • Dose-Response Relationship, Drug
  • Epilepsy (chemically induced, prevention & control)
  • Female
  • Humans
  • Injections, Intraperitoneal
  • Kindling, Neurologic
  • Male
  • Pentylenetetrazole
  • Rats (growth & development)
  • Receptors, GABA (drug effects)

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