Ifenprodil, an antagonist of NMDA receptors containing the NR2B subunit, was expected to exhibit anticonvulsant action in rat pups up to the third postnatal week because of predominance of NR2B subunit at early development. Cortical epileptic afterdischarges (ADs) were used to study possible effects on threshold current intensities and duration of ADs in 12-, 15-, 18-, and 25-day-old rats. A series of 18 stimulation series with stepwise increasing current intensities (from 0.2 to 15 mA) was applied with 10-min intervals. The first experiment studied rats pretreated with ifenprodil (20 or 40 mg/kg), the second experiment studied an effect of ifenprodil on already present ADs-the dose of 20 mg/kg was administered after stimulation with the 3.5-mA current intensity. Pretreatment with ifenprodil resulted in an anticonvulsant effect in 15-day-old rats only, on the contrary, proconvulsant action was found in 18- and 25-day-old animals (decrease of thresholds especially for transition into the second, limbic type of ADs and increase in duration of ADs). Anticonvulsant effect was found in 12-, 15-, and 18-day-old rats in the second experiment-ADs were shortened. In contrast, no effect was observed in 25-day-old animals. An anticonvulsant action of ifenprodil is not only age-dependent but also activation-dependent.

Department of Developmental Epileptology Institute of Physiology Academy of Sciences of the Czech Republic Videnska 1083 14220 Prague 4 Czech Republic

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Nat Rev Neurosci. 2013 Jun;14(6):383-400 PubMed

Neuropharmacology. 2004 Dec;47(7):1008-20 PubMed

Psychopharmacology (Berl). 2002 Aug;162(4):364-72 PubMed

Physiol Res. 2004;53 Suppl 1:S115-24 PubMed

Epilepsy Res. 2005 Mar-Apr;64(1-2):23-30 PubMed

Mol Pharmacol. 1993 Oct;44(4):851-9 PubMed

Behav Brain Res. 2012 Feb 1;227(1):276-86 PubMed

J Physiol. 1996 Dec 15;497 ( Pt 3):761-72 PubMed

J Biol Chem. 1996 Apr 19;271(16):9603-11 PubMed

Arch Int Pharmacodyn Ther. 1990 Sep-Oct;307:49-59 PubMed

Behav Brain Res. 2003 Mar 18;140(1-2):1-47 PubMed

Curr Opin Pharmacol. 2006 Feb;6(1):68-74 PubMed

Curr Med Chem. 2001 Sep;8(11):1275-89 PubMed

Eur J Pharmacol. 2001 Mar 30;416(3):185-95 PubMed

Eur J Pharmacol. 1999 Apr 29;371(2-3):147-52 PubMed

Curr Drug Targets. 2001 Sep;2(3):273-83 PubMed

Brain Res Dev Brain Res. 1994 Aug 12;81(1):105-12 PubMed

Neuropharmacology. 2013 Nov;74:4-17 PubMed

Brain Res. 2011 Sep 15;1412:102-7 PubMed

Epilepsy Behav. 2011 Dec;22(4):617-40 PubMed

J Neurochem. 1997 Feb;68(2):469-78 PubMed

J Pharmacol Exp Ther. 1997 Dec;283(3):1285-92 PubMed

Exp Neurol. 1986 Sep;93(3):546-56 PubMed

Eur J Pharmacol. 1992 Jan 28;211(1):105-8 PubMed

Epilepsy Behav. 2009 Jan;14(1):32-9 PubMed

Brain Res Dev Brain Res. 1997 Dec 19;104(1-2):201-4 PubMed

Epilepsy Res. 2004 Mar;59(1):43-50 PubMed

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