TY - JOUR
T1 - Lamotrigine derivatives and riluzole inhibit INa,P in cortical neurons
AU - Spadoni, Francesca
AU - Hainsworth, Atticus Henry
AU - Mercuri, Nicola Biagio
AU - Caputi, Luigi
AU - Martella, Giuseppina
AU - Lavaroni, Franco
AU - Bernardi, Giorgio
AU - Stefani, Alessandro
PY - 2002/7/2
Y1 - 2002/7/2
N2 - The persistent, slowly inactivating fraction of the sodium current is involved in key functions in the CNS such as dendritic integration of synaptic inputs and cellular excitability. We have studied whether established anti-epileptic drugs and neuroprotective agents target the persistent sodium current. Two lamotrigine derivatives (sipatrigine and 202W92) and riluzole inhibited the persistent sodium current at low, therapeutic concentrations. In contrast, lamotrigine and the classical antiepileptic agents phenytoin and valproic acid blocked the fast-inactivating sodium channel but failed to affect the persistent fraction. The ability to influence either mode of channel activaty may represent a defining feature of each drug sub-class, changing profoundly their clinical indications. Given the damaging role of a sustained influx of sodium in both pharmaco-resistant seizures or excitotoxic insults, we suggest the utilization of drugs that suppress the persistent conductance.
AB - The persistent, slowly inactivating fraction of the sodium current is involved in key functions in the CNS such as dendritic integration of synaptic inputs and cellular excitability. We have studied whether established anti-epileptic drugs and neuroprotective agents target the persistent sodium current. Two lamotrigine derivatives (sipatrigine and 202W92) and riluzole inhibited the persistent sodium current at low, therapeutic concentrations. In contrast, lamotrigine and the classical antiepileptic agents phenytoin and valproic acid blocked the fast-inactivating sodium channel but failed to affect the persistent fraction. The ability to influence either mode of channel activaty may represent a defining feature of each drug sub-class, changing profoundly their clinical indications. Given the damaging role of a sustained influx of sodium in both pharmaco-resistant seizures or excitotoxic insults, we suggest the utilization of drugs that suppress the persistent conductance.
KW - Lamotrigine derivatives
KW - Neuroprotective agents
KW - Pharmacology of sodium channel
KW - Riluzole
KW - Slowly inactivating sodium current
UR - http://www.scopus.com/inward/record.url?scp=0037007984&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037007984&partnerID=8YFLogxK
M3 - Article
C2 - 12151762
AN - SCOPUS:0037007984
VL - 13
SP - 1167
EP - 1170
JO - NeuroReport
JF - NeuroReport
SN - 0959-4965
IS - 9
ER -