International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(12), P. 6804 - 6804
Published: June 20, 2024
NMDA
receptor
antagonists
have
potential
for
therapeutics
in
neurological
and
psychiatric
diseases,
including
neurodegenerative
epilepsy,
traumatic
brain
injury,
substance
abuse
disorder
(SUD),
major
depressive
(MDD).
(S)-ketamine
was
the
first
of
a
novel
class
antidepressants,
rapid-acting
to
be
approved
medical
use.
The
stereoisomer,
(R)-ketamine
(arketamine),
is
currently
under
development
treatment-resistant
depression
(TRD).
compound
has
demonstrated
efficacy
multiple
animal
models.
Two
clinical
studies
disclosed
TRD
bipolar
depression.
A
study
by
drug
sponsor
recently
failed
reach
priori
endpoints
but
post
hoc
analysis
revealed
efficacy.
value
supported
experimental
data
humans
rodents,
showing
that
it
less
sedating,
does
not
produce
marked
psychotomimetic
or
dissociative
effects,
than
(S)-ketamine,
produces
models
range
disorders.
mechanisms
action
antidepressant
effects
are
hypothesized
due
antagonism
and/or
non-NMDA
mechanisms.
We
suggest
further
experimentation
with
will
create
improved
medicines
some
disorders
underserved
current
medications.
Brain Research Bulletin,
Journal Year:
2022,
Volume and Issue:
182, P. 44 - 56
Published: Feb. 11, 2022
Depression
is
the
most
common
mental
disorder
and
a
leading
cause
of
disability
worldwide.
Despite
abundant
research,
precise
mechanisms
underlying
pathophysiology
depression
remain
elusive.
Accumulating
evidence
from
preclinical
clinical
studies
suggests
that
alterations
in
gut
microbiota,
microbe-derived
short-chain
fatty
acids,
D-amino
acids
metabolites
play
key
role
via
brain–gut–microbiota
axis,
including
neural
immune
systems.
Notably,
axis
might
crucial
susceptibility
versus
resilience
rodents
exposed
to
stress.
Vagotomy
reported
block
depression-like
phenotypes
after
fecal
microbiota
transplantation
"depression-related"
microbiome,
suggesting
vagus
nerve
influences
through
axis.
In
this
article,
we
review
recent
findings
regarding
discuss
its
potential
as
therapeutic
target
for
depression.
Neuropsychopharmacology,
Journal Year:
2023,
Volume and Issue:
49(1), P. 41 - 50
Published: July 24, 2023
Abstract
Ketamine
is
an
open
channel
blocker
of
ionotropic
glutamatergic
N
-Methyl-
D
-Aspartate
(NMDA)
receptors.
The
discovery
its
rapid
antidepressant
effects
in
patients
with
depression
and
treatment-resistant
fostered
novel
effective
treatments
for
mood
disorders.
This
not
only
provided
new
insight
into
the
neurobiology
disorders
but
also
uncovered
fundamental
synaptic
plasticity
mechanisms
that
underlie
treatment.
In
this
review,
we
discuss
key
clinical
aspects
ketamine’s
effect
as
a
rapidly
acting
antidepressant,
circuit
underlying
action,
well
how
these
perspectives
practice
synapse
biology
form
road
map
future
studies
aimed
at
more
neuropsychiatric
European Archives of Psychiatry and Clinical Neuroscience,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 27, 2024
The
growing
interest
in
the
rapid
and
sustained
antidepressant
effects
of
dissociative
anesthetic
ketamine
classic
psychedelics,
such
as
psilocybin,
is
remarkable.
However,
both
psychedelics
are
known
to
induce
acute
mystical
experiences;
can
cause
symptoms
out-of-body
experience,
while
typically
bring
about
hallucinogenic
experiences,
like
a
profound
sense
unity
with
universe
or
nature.
role
these
experiences
enhancing
outcomes
for
patients
depression
currently
an
area
ongoing
investigation
debate.
Clinical
studies
have
shown
that
following
administration
(S)-ketamine
(esketamine)
not
directly
linked
their
properties.
In
contrast,
potential
(R)-ketamine
(arketamine),
thought
lack
side
effects,
has
yet
be
conclusively
proven
large-scale
clinical
trials.
Moreover,
although
activation
serotonin
5-HT
Neuropharmacology,
Journal Year:
2022,
Volume and Issue:
218, P. 109219 - 109219
Published: Aug. 14, 2022
The
N-methyl-d-aspartate
receptor
(NMDAR)
antagonist
(R,S)-ketamine
causes
rapid
onset
and
sustained
antidepressant
actions
in
treatment-resistant
patients
with
major
depressive
disorder
(MDD)
other
psychiatric
disorders,
such
as
bipolar
post-traumatic
stress
disorder.
is
a
racemic
mixture
consisting
of
(R)-ketamine
(or
arketamine)
(S)-ketamine
esketamine),
(S)-enantiomer
having
greater
affinity
for
the
NMDAR.
In
2019,
an
esketamine
nasal
spray
by
Johnson
&
was
approved
USA
Europe
depression.
contrast,
increasing
number
preclinical
studies
show
that
arketamine
has
potency
longer-lasting
antidepressant-like
effects
than
rodents,
despite
lower
binding
Importantly,
side
effects,
i.e.,
psychotomimetic
dissociative
abuse
liability,
are
less
those
animals
humans.
An
open-label
study
demonstrated
MDD.
A
phase
2
clinical
trial
MDD
underway.
This
designed
to
review
brief
history
novel
arketamine,
molecular
mechanisms
underlying
its
actions,
future
directions.
article
part
Special
Issue
on
'Ketamine
Metabolites'.
MedComm,
Journal Year:
2022,
Volume and Issue:
3(3)
Published: July 21, 2022
Major
depressive
disorder
(MDD)
is
a
highly
prevalent
and
disabling
disorder.
Despite
the
many
hypotheses
proposed
to
understand
molecular
pathophysiology
of
depression,
it
still
unclear.
Current
treatments
for
depression
are
inadequate
individuals,
because
limited
effectiveness,
delayed
efficacy
(usually
two
weeks),
side
effects.
Consequently,
novel
drugs
with
increased
speed
action
effectiveness
required.
Ketamine
has
shown
have
rapid,
reliable,
long-lasting
antidepressant
effects
in
treatment-resistant
MDD
patients
represent
breakthrough
therapy
MDD;
however,
concerns
regarding
its
efficacy,
potential
misuse,
remain.
In
this
review,
we
aimed
summarize
mechanisms
pharmacological
depression.
We
focused
on
fast
treatment
clarified
safety,
tolerability,
ketamine
metabolites
treatment,
along
review
mechanisms,
research
challenges,
future
clinical
prospects.
Biomedicine & Pharmacotherapy,
Journal Year:
2022,
Volume and Issue:
150, P. 113030 - 113030
Published: April 26, 2022
Depression
is
a
common
neuropsychiatric
disorder
characterized
by
persistent
depressed
mood
and
causes
serious
socioeconomic
burden
worldwide.
Hyperactivity
of
the
hypothalamic-pituitary-adrenal
(HPA)
axis,
deficiency
monoamine
transmitters,
neuroinflammation
abnormalities
gut
flora
are
strongly
associated
with
onset
depression.
The
cyclic
AMP
(cAMP)/protein
kinase
A
(PKA)
cascade,
major
cross-species
cellular
signaling
pathway,
supposed
as
important
player
regulator
depression
controlling
synaptic
plasticity,
cytokinesis,
transcriptional
regulation
HPA
axis.
In
central
nervous
system,
cAMP-PKA
cascade
can
dynamically
shape
neural
circuits
enhancing
affect
K+
channels
phosphorylating
Kir4.1,
thereby
regulating
neuronal
excitation.
reduction
affects
excitation
well
ultimately
leading
to
pathological
outcome
depression,
while
activation
would
provide
rapid
antidepressant
effect.
this
review,
we
proposed
reconsider
function
especially
in
Local
or
indirect
PKA
through
adjusting
anchor
proteins
new
idea
for
acute
treatment
Neurobiology of Disease,
Journal Year:
2022,
Volume and Issue:
165, P. 105635 - 105635
Published: Jan. 24, 2022
Multiple
sclerosis
(MS)
is
the
most
common
demyelinating
disease
that
attacks
central
nervous
system.
We
recently
reported
new
antidepressant
(R)-ketamine
could
ameliorate
progression
in
experimental
autoimmune
encephalomyelitis
model
of
MS.
Cuprizone
(CPZ)
has
been
used
to
produce
demyelination
which
resembles
MS
patients.
This
study
was
undertaken
investigate
whether
affect
CPZ-treated
mice
and
remyelination
after
CPZ
withdrawal.
Repeated
treatment
with
(10
mg/kg/day,
twice
weekly,
for
6
weeks)
significantly
ameliorated
activated
microglia
brain
compared
saline-treated
mice.
Furthermore,
pretreatment
ANA-12
(TrkB
antagonist)
blocked
beneficial
effects
on
The
16S
rRNA
analysis
showed
improved
abnormal
composition
gut-microbiota
decreased
levels
lactic
acid
In
addition,
there
were
significant
correlations
between
(or
microglial
activation)
relative
abundance
several
microbiome,
suggesting
a
link
gut
microbiota
brain.
Interestingly,
facilitate
conclusion,
suggests
through
TrkB
activation,
gut-microbiota-microglia
crosstalk
may
play
role
Therefore,
it
likely
be
therapeutic
drug
