Biomedical Engineering Reference
In-Depth Information
NH
2
OH
H
2
N
O
O
O
NH
H
3
C
F
O
N
NH
2
Cl
remacemide
safinamide
α
-hydroxyphenylamide
Fig. 8 Sodium channel blockers
3.3.5 Psychiatric Disorders
Several compounds among the anticonvulsant class have played a major role in
therapeutic approaches to bipolar illness and other psychiatric disorders such as
schizophrenia [
95
,
211
,
212
]. As specified in Sect.
2.4.7
, genes encoding for
different VGSCs seems to have a role in BPD and other psychiatric disorders;
nevertheless, it is very difficult to believe that the block of sodium channels
expressed in key regions of the limbic system is the only mechanism of action of
these drugs and other candidate mechanisms should be explored [
211
].
Carbamazepine and lamotrigine are the only sodium channel blockers with a
FDA indication for the treatment of psychiatric disorders (Fig.
3
)[
213
]. In particu-
lar, carbamazepine was approved as a treatment for acute mania and depression in
2004, while lamotrigine has been approved as maintenance treatment of BPD and
they seem also be efficacious for neuroleptic-resistant schizophrenia [
214
-
218
].
Other sodium channel blockers, such as oxcarbazepine, topiramate, and zonisamide
stabilize mood in bipolar and schizoaffective disorders (Figs.
3
and
4
)[
219
-
222
].
Finally, a Newron compound having sodium channel blocker properties, NW-3509,
showed efficacy in a broad spectrum of rodent models of psychosis, mania, depres-
sion, and aggressiveness. Used in combination with current antipsychotics, NW-
3509 may improve their efficacy allowing a decrease of both their dosage and side
effects [
223
].
3.3.6 Cancer
Cancers are among the leading causes of death in the world, arising from genetic
alterations and/or epigenetic changes [
224
-
226
]. At the moment, the therapeutic
strategies available include the excision of the primary tumor, when cancer is at an
early stage, followed by chemo- and/or radiotherapy. Nevertheless, this strategy is
often not decisive, and it can lead to a reemergence of tumors after some years,
followed by the develop of secondary tumors [
84
,
227
]. This evolution is due to a
process named “metastatic cascade,” in which cancer cells enter blood or lymph
circulation and invade distant site, thus forming secondary tumors.
The ion channels are new attractive targets studied for cancer therapy and, in
particular, VGSCs, that have been shown to be involved in different aspects of the
