GABA(B) receptors mediate inhibition at early stages of development but mixed anti-and proconvulsant action of their agonists affecting all receptors was found in immature rats. Positive allosteric modulators of GABA(B) receptors potentiate only already active GABA(B) receptors and therefore more specific action is expected. Possible anticonvulsant action of CGP7930 was studied in a model of pentetrazol-induced seizures previously used for studies with agonists baclofen and SKF97541. Pentetrazol (100mg/kg) was administered subcutaneously in male rats 7, 12, 18, 25 and 90 days old pretreated with CGP7930 in doses 1-40 mg/kg i.p. High doses of CGP7930 suppressed generalized tonic-clonic seizures in all five age groups. Animals 18 and less days old exhibited a specific suppression of the tonic phase after lower doses of CGP7930. Twelve-day-old rats were the most sensitive to anticonvulsant effect of CGP7930 (even the 2-mg/kg dose suppressed the tonic phase whereas 20-mg/kg dose was active in other age groups). Minimal clonic seizures (mS) were moderately potentiated by low doses of CGP7930 in 18-day-old but suppressed by the highest dose in 25-day-old rats. The 60-mg/kg dose of PTZ induced only mS in 4 out of 9 25-day-old rats; the 40-mg/kg dose of CGP7930 combined with this lower dose of PTZ resulted in the only proconvulsant effect--generalized tonic-clonic seizures appeared in two rats. Results from 12-day-old rats suggest a possibility to find an age-specific anticonvulsant among positive allosteric modulators of GABA(B) receptors.

Department of Developmental Epileptology Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic

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Anticonvulsant Action of GluN2A-Preferring Antagonist PEAQX in Developing Rats