Biomedical Engineering Reference
In-Depth Information
Zonisamide (Fig.
3
): zonisamide is chemically unrelated to any of the other
AEDs. It was approved in the USA for the treatment of partial seizures in adults.
The principle mechanism of action of zonisamide seems to be the block of the
repetitive firing of VGSCs and the reduction of the T-type calcium currents. It is
effective not only in adult focal epilepsies, but also it may represent an option in the
difficult-to-treat epilepsy syndromes. Moreover, its favorable pharmacokinetic
characteristics and its broad range of mechanism of action turns zonisamide into
an important tool in combined therapy with other AEDs [
95
,
97
].
Valproate (Fig.
3
): valproate is an AED introduced in the 1970s, which has an
exceptionally broad range of anticonvulsant efficacy: it is effective against partial
and generalized tonic-clonic seizures, absence seizures, and myoclonic seizures
[
98
]. The mechanism of action of valproate remains undefined, but it is evident that
VGSCs are among the brain targets hit by the drug [
98
].
Lamotrigine (Fig.
3
): lamotrigine represents an effective treatment for partial
and generalized tonic-clonic seizures and also for the management of absence
attacks in primary generalized epilepsies [
95
]. As for phenytoin, the demonstrated
efficacy of lamotrigine in clinical practice is primarily due to its ability to block
both in a voltage-dependent and in a frequency-dependent manner the VGSCs.
However, its effectiveness cannot depend only on VGSC inhibition, but its capa-
bility to manage absences is probably due to its action on different targets [
99
,
100
].
Topiramate (Fig.
3
): topiramate is characterized by a phenytoin-like profile in
maximal electroshock seizure and pentetrazol tests, and it presumably acts by
depressing sustained repetitive firing and voltage-gated Na
+
currents [
101
]. How-
ever, topiramate antiepileptic effects may not depend exclusively on VGSCs
blockade and it probably exerts its effect by others mechanisms, comprising the
interaction with excitatory amino acid transmission [
102
,
103
].
Riluzole (Fig.
3
): riluzole was at first developed as an AED but approved for the
treatment of amyotrophic lateral sclerosis. Its mechanism of action is most likely
related to its antiglutamatergic properties; however,
this drug has also been
characterized as a classic VGSC blocker [
104
].
Lacosamide (Fig.
3
): lacosamide is effective in patients with uncontrolled partial
seizures and demonstrates an important efficacy in controlling seizure activity in
several in vivo and in vitro models of epilepsy [
105
]. Lacosamide inhibits VGSCs
by enhancing channel slow inactivation [
106
]. Voltage-clamp experiments have
also revealed that this drug decreases the frequency of both inhibitory and excit-
atory postsynaptic currents without influencing membrane passive properties [
107
].
Therefore, lacosamide targets VGSCs, although with a different mechanism respect
to phenytoin and carbamazepine.
3.2 As Pain-Relieving Drugs
Pain is a complex sensory phenomenon characterized according to duration (acute
or chronic),
intensity (mild, moderate, or severe), and type (nociceptive,
