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.