Abstracts

ucb 34714 is a new pyrrolidone derivative (Kenda [italic]et al.[/italic], [italic]J. Med. Chem.[/italic] [underline]47[/underline], 530, 2004) structurally related to levetiracetam, with significant antiepileptic activity in preclinical epilepsy models [italic]in vitro[/italic] (Margineanu [italic]et al[/italic].,[italic] Epilepsia[/italic] [underline]44[/underline], Suppl. 9, 261, 2003) and [italic]in vivo[/italic] (Matagne [italic]et al[/italic].,[italic] Epilepsia[/italic] [underline]44[/underline], Suppl. 9, 260, 2003). Since levetiracetam was reported to inhibit HVA calcium currents in rat hippocampal neurons (Niespodziany [italic]et al[/italic]., [italic]Neurosci. Lett. [/italic][underline]306[/underline], 5-8, 2001; Lukyanetz [italic]et al[/italic].,[italic] Epilepsia[/italic] [underline]43[/underline], 9-18, 2002), this study explored the potential activity of ucb 34714 on neuronal high- and low-voltage activated calcium currents. The effects of ucb 34714 on voltage activated calcium channels were studied in acutely isolated rat neurons, by whole-cell patch-clamp recordings. The high-voltage activated (HVA) Ca²⁺ currents were recorded on hippocampal CA1 neurons from 14 day-old rats; the low-voltage activated (LVA) Ca²⁺ currents were recorded on dorsal root ganglia (DRG) neurons from 1 [ndash] 2 month-old rats. ucb 34714, 0.1 [micro]M [ndash] 1 mM did not influence the HVA calcium current, with respect to maximal amplitude, voltage dependence, kinetics of activation and inactivation, and run-down during experimental protocols up to 20 min. Also, ucb 34714,1 [micro]M [ndash] 2 mM did not influence the LVA calcium current with respect to maximal amplitude, voltage dependence, and kinetics of activation and inactivation. This study shows that ucb 34714 is without impact on voltage activated calcium channels in acutely isolated rat neurons. (Supported by UCB Pharma, Belgium)