The Annual Review of Pharmacology and Toxicology,
Год журнала:
2023,
Номер
64(1), С. 277 - 289
Опубликована: Авг. 8, 2023
Cholinergic
regulation
of
dopamine
(DA)
signaling
has
significant
implications
for
numerous
disorders,
including
schizophrenia,
substance
use
and
mood-related
disorders.
The
activity
midbrain
DA
neurons
release
patterns
in
terminal
regions
are
tightly
regulated
by
cholinergic
found
both
the
striatum
hindbrain.
These
can
modulate
circuitry
activating
receptors,
muscarinic
acetylcholine
receptor
(mAChR)
subtypes.
This
review
specifically
focuses
on
complex
role
M2,
M4,
M5
mAChR
subtypes
regulating
neuron
potential
clinical
targeting
these
Molecular Psychiatry,
Год журнала:
2023,
Номер
28(5), С. 1902 - 1918
Опубликована: Янв. 23, 2023
Abstract
Cognitive
deficits
are
a
core
feature
of
schizophrenia,
account
for
much
the
impaired
functioning
associated
with
disorder
and
not
responsive
to
existing
treatments.
In
this
review,
we
first
describe
clinical
presentation
natural
history
these
deficits.
We
then
consider
aetiological
factors,
highlighting
how
range
similar
genetic
environmental
factors
both
cognitive
function
schizophrenia.
review
pathophysiological
mechanisms
thought
underlie
symptoms,
including
role
dopamine,
cholinergic
signalling
balance
between
GABAergic
interneurons
glutamatergic
pyramidal
cells.
Finally,
management
impairments
candidate
novel
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Апрель 9, 2024
Abstract
G
protein-coupled
receptors
(GPCRs),
the
largest
family
of
human
membrane
proteins
and
an
important
class
drug
targets,
play
a
role
in
maintaining
numerous
physiological
processes.
Agonist
or
antagonist,
orthosteric
effects
allosteric
effects,
biased
signaling
balanced
signaling,
characterize
complexity
GPCR
dynamic
features.
In
this
study,
we
first
review
structural
advancements,
activation
mechanisms,
functional
diversity
GPCRs.
We
then
focus
on
discovery
by
revealing
detailed
drug-target
interactions
underlying
mechanisms
drugs
approved
US
Food
Drug
Administration
past
five
years.
Particularly,
up-to-date
analysis
is
performed
available
structures
complexed
with
synthetic
small-molecule
modulators
to
elucidate
key
receptor-ligand
mechanisms.
Finally,
highlight
how
widespread
GPCR-druggable
sites
can
guide
structure-
mechanism-based
design
propose
prospects
designing
bitopic
ligands
for
future
therapeutic
potential
targeting
receptor
family.
Biological Psychiatry,
Год журнала:
2024,
Номер
96(8), С. 627 - 637
Опубликована: Март 25, 2024
Achieving
optimal
treatment
outcomes
for
individuals
living
with
schizophrenia
remains
challenging,
despite
70
years
of
drug
development
efforts.
Many
chemically
distinct
antipsychotics
have
been
developed
over
the
past
seven
decades
improved
safety
and
tolerability
but
only
slight
variation
in
efficacy.
All
currently
prescribed
act
as
antagonists
or
partial
agonists
at
dopamine
D2
receptor.
With
a
few
possible
exceptions,
antipsychotic
drugs
similar
modest
efficacy
treating
positive
symptoms
are
relatively
ineffective
addressing
negative
cognitive
disease.
The
novel
treatments
focused
on
targeting
muscarinic
acetylcholine
receptors
(mAChRs)
has
interest
more
than
25
following
reports
that
dual
M1/M4
preferring
mAChR
agonist
resulted
antipsychotic-like
effects
procognitive
properties
Alzheimer's
disease
schizophrenia;
recent
clinical
trials
confirmed
these
findings.
In
addition,
advances
our
understanding
receptor
binding
activation
xanomeline
specific
mAChRs
potential
to
inform
future
design
mAChRs.
Biomedicines,
Год журнала:
2024,
Номер
12(3), С. 613 - 613
Опубликована: Март 8, 2024
Neuroscience,
neurology,
and
psychiatry
are
rapidly
evolving
fields
that
aim
to
understand
the
complex
mechanisms
underlying
brain
function
dysfunction,
as
well
develop
effective
interventions
for
various
neurological
psychiatric
disorders
[...]
Delve
into
the
dynamic
realms
of
neuroscience,
neurology,
and
psychiatry
with
this
groundbreaking
editorial,
unveiling
intricate
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brain
function
dysfunction.
Explore
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advancements
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pharmacology,
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that
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revolutionizing
our
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neurological
psychiatric
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Uncover
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translating
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practical
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Discover
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reshaping
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Schizophrenia Bulletin Open,
Год журнала:
2024,
Номер
5(1)
Опубликована: Янв. 1, 2024
Abstract
Cognitive
Impairment
Associated
with
Schizophrenia
(CIAS)
represents
one
of
the
core
dimensions
Spectrum
Disorders
(SSD),
an
important
negative
impact
on
real-world
functional
outcomes
people
living
SSD.
Treatment
CIAS
a
therapeutic
goal
considerable
importance,
and
while
cognition-oriented
evidence-based
psychosocial
interventions
are
available,
effective
pharmacological
treatment
could
represent
game-changer
in
lives
The
present
critical
review
reports
discusses
evidence
regarding
effects
several
agents
that
available
clinical
practice
or
under
study,
commenting
both
current
future
perspectives
treatment.
In
particular,
antipsychotic
medications,
anticholinergic
benzodiazepines,
which
currently
commonly
used
SSD,
iclepertin,
d-serine,
luvadaxistat,
xanomeline-trospium,
ulotaront,
anti-inflammatory
molecules,
oxytocin,
undergoing
regulatory
trials
can
be
considered
as
experimental
agents,
will
reported
discussed.
Currently,
do
not
appear
to
provide
substantial
benefits
CIAS,
but
accurate
management
medications
avoiding
treatments
further
exacerbate
strategies.
Some
molecules
being
investigated
Phase
2
3
have
provided
very
promising
preliminary
results,
more
information
is
required
assess
their
effectiveness
contexts
clear
recommendations
use
practice.
results
ongoing
studies
reveal
whether
any
these
awaited
CIAS.
