Revista de Neurología,
Год журнала:
2024,
Номер
79(06), С. 161 - 161
Опубликована: Янв. 1, 2024
This
review,
conducted
by
the
Andalusian
Epilepsy
Society,
provides
an
update
on
recent
advances
in
treatment
of
drug-resistant
epilepsy,
focusing
three
new
anti-seizure
drugs:
cenobamate,
fenfluramine
and
cannabidiol.
These
emerging
drugs
offer
therapeutic
alternatives
for
patients
with
focal
Dravet
syndrome,
Lennox-Gastaut
syndrome.
The
primary
objective
this
review
is
to
provide
healthcare
professionals
up-to-date
overview
efficacy,
safety
potential
clinical
applications
these
treatments,
backed
latest
evidence.
In
addition
reviewing
available
evidence,
document
addresses
essential
practical
considerations
implementation
routine
practice,
including
aspects
such
as
their
dosage,
drug
interactions,
management
side-effects.
With
Society
aims
contribute
improving
care
quality
life
epilepsy
families.
Pharmacology & Therapeutics,
Год журнала:
2025,
Номер
unknown, С. 108808 - 108808
Опубликована: Фев. 1, 2025
Out
of
37
antiseizure
medications
(ASMs)
currently
in
the
market,
17
are
chiral
molecules
and
an
additional
one
(oxcarbazepine)
is
a
prodrug
compound
licarbazepine.
Of
ASMs,
six
(ethosuximide,
fenfluramine,
methsuximide,
mephobarbital,
stiripentol
vigabatrin)
marketed
as
racemates,
remainder
licensed
enantiomerically
pure
medicines.
note,
all
ASMs
introduced
prior
to
1990
were
racemates.
Stiripentol,
fenfluramine
vigabatrin
only
racemic
approved
by
FDA
>10
years
after
release
regulatory
guidelines
on
development
Despite
fact
that
pharmacokinetic
pharmacodynamic
differences
between
enantiomers
have
been
recognized
for
decades,
importance
chirality
understanding
biological
actions
not
widely
appreciated,
many
recent
publications
refer
these
if
they
single
molecular
entity.
In
present
article,
we
provide
critical
review
developed
1920s,
when
mephobarbital
was
introduced,
2022,
last
ASM
(ganaxolone)
approved.
We
summarize
available
data
stereoselective
pharmacokinetics
pharmacodynamics
also
discuss
aspects
related
introduction
medicines
within
current
scenario
Europe
U.S.,
focusing
stiripentol,
examples
different
approaches.
identified
number
knowledge
gaps
relevant
use
drugs
epilepsy,
including
remarkable
lack
published
information
comparative
pharmacokinetics,
toxicity
activity
most
ASMs.
The
clinical
discussed,
together
with
rationale
follow-up
compounds
potentially
improved
efficacy,
safety
commercial
viability.
Epilepsia Open,
Год журнала:
2024,
Номер
9(5), С. 1643 - 1657
Опубликована: Июль 4, 2024
Abstract
Fenfluramine
(FFA),
an
antiseizure
medication
(ASM)
with
serotonergic
and
sigma‐1
receptor
activity,
is
used
to
manage
patients
developmental
epileptic
encephalopathies
(DEEs).
It
approved
in
the
US
for
treating
seizures
associated
Dravet
syndrome
(DS)
Lennox–Gastaut
(LGS)
≥2
years
old
as
add‐on
therapy
DS
LGS
EU,
UK,
Japan
similarly
aged
patients.
Consensus
guidelines
treatment
of
have
recommended
FFA
be
early‐line
ASM,
it
has
also
shown
efficacy
managing
LGS.
are
DEEs
a
range
seizure
types,
impairments,
multiple
comorbidities.
Here
we
provide
case
vignettes
describing
4
(3
1
LGS)
4–29
whom
up
14
ASMs
had
previously
failed,
illustrate
real‐world
practice
issues
encountered
by
neurologists.
This
review
provides
guidance
on
use
context
ASM
polytherapy
drug–drug
interactions
(DDIs),
behavioral
issues,
dose
titration,
adverse
events.
Along
data
from
clinical
trial
program,
these
emphasize
low
risk
DDIs,
generally
well‐tolerated
safety
profile,
other
nonseizure
benefits
(eg,
improved
cognition
sleep)
or
Plain
Language
Summary
treat
individuals
syndrome,
but
there
that
clinicians
may
face
when
highlights
four
authors’
everyday
work
offers
practical
considerations
neurologists
expertise
complex
conditions
related
drug
interactions,
dosing,
side
effects
fenfluramine.
Neurological Research and Practice,
Год журнала:
2024,
Номер
6(1)
Опубликована: Фев. 22, 2024
Novel
treatments
are
needed
to
control
refractory
status
epilepticus
(SE).
This
study
aimed
assess
the
potential
effectiveness
of
fenfluramine
(FFA)
as
an
acute
treatment
option
for
SE.
We
present
a
summary
clinical
cases
where
oral
FFA
was
used
in
Deleted Journal,
Год журнала:
2024,
Номер
37(1), С. 68 - 78
Опубликована: Янв. 3, 2024
Abstract
Fenfluramine
is
an
antiseizure
medication
for
the
treatment
of
Dravet
and
Lennox–Gastaut
syndromes.
This
review
summarizes
literature
on
efficacy
tolerability
fenfluramine
presents
recommendations
practical
therapeutic
management.
With
regular
monitoring,
this
generally
well
tolerated
to
date
has
shown
no
cardiac
side
effects
such
as
valve
insufficiency
or
pulmonary
hypertension
in
clinical
development
program.
However,
children
may
experience
a
loss
appetite
should
be
closely
monitored
weight
loss,
sedation
was
observed
several
overweight
patients
due
rapid
dosage
titration;
therefore,
slower
increase
than
recommended
might
needed
adults.
Drug
interactions
considered
before
during
therapy,
reductions
are
necessary
when
used
combination
with
stiripentol.
Furthermore,
bromide
levels
could
medication.
Contact
patient
their
relatives
important
determine
general
state
health,
potential
movement
disturbances,
seizure
frequency
so
allow
timely
adjustments
titration
phase.
Expert Opinion on Pharmacotherapy,
Год журнала:
2024,
Номер
25(9), С. 1121 - 1130
Опубликована: Июнь 12, 2024
Developmental
epileptic
encephalopathies
(DEEs)
pose
significant
challenges
due
to
their
refractory
nature
and
limited
treatment
options.
Despite
advancements
in
genetic
understanding,
effective
therapies
targeting
underlying
pathophysiology
are
lacking.
Serotoninergic
dysfunction
has
been
implicated
epilepsy,
sparking
interest
serotonin
as
a
therapeutic
target.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(5), С. 2991 - 2991
Опубликована: Март 4, 2024
The
zebrafish
model
has
emerged
as
a
reference
tool
for
phenotypic
drug
screening.
An
increasing
number
of
molecules
have
been
brought
from
bench
to
bedside
thanks
zebrafish-based
assays
over
the
last
decade.
high
homology
between
and
human
genomes
facilitates
generation
lines
carrying
loss-of-function
mutations
in
disease-relevant
genes;
nonetheless,
even
using
this
alternative
model,
establishment
isogenic
mutant
requires
long
time
an
elevated
animals.
In
study,
we
developed
high-throughput
platform
F0
knock-out
(KO)
models
screening
neuroactive
compounds.
We
show
that
simultaneous
inactivation
reporter
gene
(tyrosinase)
second
interest
allows
selection
somatic
mutants
(crispants)
highest
rates
both
loci.
As
proof
principle,
targeted
genes
associated
with
neurodevelopmental
disorders
efficiently
generated
de
facto
seven
involved
childhood
epilepsy.
employed
multiparametric
behavioral
analysis
characterize
response
these
KO
epileptogenic
stimulus,
making
it
possible
employ
kinematic
parameters
identify
seizure-like
events.
combination
co-injection,
phenotyping
methods
allowed
us
generate
crispants
recapitulating
epilepsy
features
test
efficacy
compounds
already
during
first
days
post
fertilization.
Since
strategy
can
be
applied
wide
range
indications,
study
paves
ground
discovery
promotes
use
personalized
medicine
neurotoxicity
assessment.
Epilepsia Open,
Год журнала:
2024,
Номер
9(5), С. 1891 - 1900
Опубликована: Авг. 14, 2024
Abstract
Objectives
Dravet
syndrome
is
a
developmental
and
epileptic
encephalopathy
characterized
by
early
onset
epilepsy
with
multiple
seizure
types
often
intractable
to
treatment.
Randomized
clinical
trials
have
demonstrated
how
treatment
fenfluramine
significantly
reduces
frequency
in
patients
syndrome.
The
study
aims
(1)
describe
the
efficacy
tolerability
of
Danish
cohort
syndrome;
(2)
evaluate
whether
epilepsy‐related
hospital
contacts
administrated
pediatricians
or
epilepsy‐trained
nurses.
Methods
A
retrospective
registry‐based
at
Epilepsy
Centre,
Filadelfia,
Dianalund,
Denmark,
enrolled
30
pediatric
treated
between
2017
2023.
Results
Thirty
(aged
3–21
years,
12
females)
verified
pathogenic
SCN1A
variant
were
included.
They
mean
duration
29
months
maintenance
dose
0.5
mg/kg/day.
number
patient‐years
on
was
75
years.
At
last
follow‐up,
6
had
discontinued
due
lack
adverse
effects.
In
remaining
24
patients,
generalized
tonic–clonic
seizures
reduced
≥30%
83%,
≥50%
67%,
100%
25%.
Additionally,
71%
concomitant
anti‐seizure
medication,
75%
experienced
reduction
(mean
52%,
range
11%–94%)
from
baseline
end
period.
Significance
Treatment
effectively
antiseizure
medication
Furthermore,
decrease
80%
observed
over
years
treatment,
which
may
indicate
cost‐effective
benefits.
Plain
Language
Summary
Patients
suffer
severe
that
are
difficult
treat
medication.
Earlier,
(an
medication)
has
been
documented
total
This
publication
summarizes
experiences
children
Denmark.
Our
also
illustrates
reduce
patients'
yearly
doctors
nurses
specialized
cost‐effectiveness.
