Fundamental and Clinical Pharmacology,
Год журнала:
2023,
Номер
38(1), С. 139 - 151
Опубликована: Авг. 23, 2023
Abstract
Background
Although
brimonidine
is
currently
used
in
the
clinical
treatment
of
glaucoma
and
rosacea,
research
deep
sedative
effect
on
animals
after
systemic
administration
reported
firstly
has
shown
promising
results.
Methods
The
median
effective
dose
(ED
50
),
lethal
(LD
therapeutic
index
for
sedation
formalin
stimulation
assay
were
determined
by
various
animal
experiments.
synergistic
anesthesia
rabbits
with
chloral
hydrate
was
preliminarily
evaluated.
Results
ED
highly
intraperitoneal
injection
rats
calculated
to
be
2.05
mg
kg
−1
a
95%
confidence
interval
(CI)
1.87
2.25
.
intravenous
intrarectal
0.087
CI
0.084
0.091
1.65
1.43
1.91
,
respectively.
LD
468
441
497
228.
Brimonidine
certain
analgesic
heart
rate
lowering
effects.
Conclusion
results
confirmed
that
effects
high
safety.
It
can
combination
other
types
drugs
achieve
better
The
unique
sedative
activities
with
rapid
arousal
of
dexmedetomidine
(Dex)
are
not
fully
understood.
Growing
evidence
suggests
the
involvement
ventrolateral
preoptic
area
(VLPO)
in
sleep–wake
cycle.
major
type
VLPO
is
sleep-active
neurons,
inhibited
by
noradrenaline
(NA(−)
neurons).
other
neurons
activated
NA
(NA(+)
neurons),
which
wake-active.
Previous
research
showed
that
Dex-induced
sedation
and
sleep
homeostasis
likely
share
common
mechanisms.
To
explore
underlying
mechanisms
Dex
VLPO,
vivo
polysomnography
recording
vitro
electrophysiological
were
used
our
study.
Bath
application
(2
μM)
increased
firing
rate
both
NA(−)
NA(+)
neurons.
Compared
to
control
group,
there
was
no
difference
after
RS79948
(1
mM)
administration,
an
α
2
receptor
antagonist.
No
detected
regarding
resting
membrane
potential
(RMP)
amplitude
(−)
μM).
Moreover,
significantly
reduced
frequency
miniature
inhibitory
postsynaptic
currents
(mIPSCs)
These
electrophysiology
results
consistent
behavioral
sedation,
nonrapid
eye
movement
(NREM
sleep)
expression
c-Fos
during
dark
phase
intraperitoneal
injection
(80
μg/kg).
In
conclusion,
activates
via
presynaptic
receptors.
This
mechanism
may
explain
properties
arousal.
Summary
Statement
Dexmedetomidine
important
ICU
sedative.
Activating
using
recording,
this
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(13), С. 11435 - 11449
Опубликована: Июнь 18, 2024
Enhancing
the
selectivity
of
alpha2-adrenoceptor
(α2A-AR)
agonists
remains
an
unresolved
issue.
Herein,
we
reported
design
α2A-AR
agonist
using
conformation
constraint
method,
beginning
with
medetomidine.
The
structure–activity
relationship
indicated
that
8-substituent
chromane
derivatives
exerted
most
pronounced
effect
on
agonistic
activity.
Compounds
A9
and
B9
were
identified
as
promising,
exhibiting
EC50
values
0.78
0.23
nM,
respectively.
Their
indexes
surpassed
dexmedetomidine
(DMED)
by
10–80
fold.
In
vivo
studies
demonstrated
both
dose-dependently
increased
loss
righting
reflex
in
mice,
ED50
1.54
0.138
mg/kg,
Binding
mode
calculations
mutation
suggested
indispensability
hydrogen
bond
between
ASP1283.32
agonist.
particular,
showed
no
dual
reverse
pharmacological
effect,
a
characteristic
exhibited
DMED
activation.
Anesthesiology and Perioperative Science,
Год журнала:
2024,
Номер
2(4)
Опубликована: Окт. 30, 2024
Abstract
Postoperative
cognitive
dysfunction,
a
common
neurological
complication
in
the
perioperative
period,
seriously
affects
patient
survival
and
prognosis.
Its
high
incidence
has
made
study
of
postoperative
dysfunction
challenging.
Whether
clinical
application
dexmedetomidine,
potential
neuroprotective
drug,
can
reduce
is
controversial,
although
several
mechanisms
by
which
dexmedetomidine
improves
have
been
identified;
therefore,
this
remains
an
area
need
further
exploration.
BMC Anesthesiology,
Год журнала:
2023,
Номер
23(1)
Опубликована: Окт. 2, 2023
Abstract
Background
and
objectives
Dexmedetomidine
(DEX)
is
widely
used
in
clinical
sedation
which
has
little
effect
on
cardiopulmonary
inhibition,
however
the
mechanism
remains
to
be
elucidated.
The
basal
forebrain
(BF)
a
key
nucleus
that
controls
sleep-wake
cycle.
horizontal
limbs
of
diagonal
bundle
(HDB)
one
subregions
BF.
purpose
this
study
was
examine
whether
possible
DEX
through
α2
adrenergic
receptor
BF
(HDB).
Methods
In
study,
we
investigated
effects
by
using
whole
cell
patch
clamp
recordings.
threshold
stimulus
intensity,
inter-spike-intervals
(ISIs)
frequency
action
potential
firing
neurons
were
recorded
application
(2
µM)
co-application
α
2
antagonist
phentolamine
(PHEN)
(10
µM).
Results
increased
inhibited
enlarged
inter-spike-interval
(ISI)
neurons.
These
reversed
PHEN
Conclusion
Taken
together,
our
findings
revealed
decreased
discharge
activity
neuron
via
receptors.
Fundamental and Clinical Pharmacology,
Год журнала:
2023,
Номер
38(1), С. 139 - 151
Опубликована: Авг. 23, 2023
Abstract
Background
Although
brimonidine
is
currently
used
in
the
clinical
treatment
of
glaucoma
and
rosacea,
research
deep
sedative
effect
on
animals
after
systemic
administration
reported
firstly
has
shown
promising
results.
Methods
The
median
effective
dose
(ED
50
),
lethal
(LD
therapeutic
index
for
sedation
formalin
stimulation
assay
were
determined
by
various
animal
experiments.
synergistic
anesthesia
rabbits
with
chloral
hydrate
was
preliminarily
evaluated.
Results
ED
highly
intraperitoneal
injection
rats
calculated
to
be
2.05
mg
kg
−1
a
95%
confidence
interval
(CI)
1.87
2.25
.
intravenous
intrarectal
0.087
CI
0.084
0.091
1.65
1.43
1.91
,
respectively.
LD
468
441
497
228.
Brimonidine
certain
analgesic
heart
rate
lowering
effects.
Conclusion
results
confirmed
that
effects
high
safety.
It
can
combination
other
types
drugs
achieve
better
