British Journal of Pharmacology,
Journal Year:
2022,
Volume and Issue:
179(14), P. 3875 - 3885
Published: March 17, 2022
Background
and
Purpose
Mitragynine,
the
major
alkaloid
in
Mitragyna
speciosa
(kratom),
is
a
partial
agonist
at
μ
opioid
receptor.
CYP3A‐dependent
oxidation
of
mitragynine
yields
metabolite
7‐OH
mitragynine,
more
efficacious
receptor
agonist.
While
both
can
induce
anti‐nociception
mice,
recent
evidence
suggests
that
formed
as
sufficient
to
explain
anti‐nociceptive
effects
mitragynine.
However,
ability
receptor‐dependent
respiratory
depression
has
not
yet
been
studied.
Experimental
Approach
Respiration
was
measured
awake,
freely
moving,
male
CD‐1
using
whole
body
plethysmography.
Anti‐nociception
hot
plate
assay.
Morphine,
CYP3A
inhibitor
ketoconazole
were
administered
orally.
Key
Results
The
depressant
showed
ceiling
effect,
whereby
doses
higher
than
10
mg·kg
−1
produced
same
level
effect.
In
contrast,
induced
dose‐dependent
effect
on
mouse
respiration.
At
equi‐depressant
doses,
prolonged
anti‐nociception.
Inhibition
reduced
mitragynine‐induced
without
affecting
Conclusions
Implications
Both
are
partly
due
its
metabolic
conversion
limiting
rate
into
active
results
built‐in
depression.
These
data
suggest
such
‘metabolic
saturation’
high
may
underlie
improved
safety
profile
an
analgesic.
Acta Anaesthesiologica Scandinavica,
Journal Year:
2024,
Volume and Issue:
68(5), P. 610 - 618
Published: Feb. 21, 2024
Abstract
Background
Morphine‐sparing
effects
are
often
used
to
evaluate
non‐opioid
analgesic
interventions.
The
exact
effect
that
would
warrant
the
implementation
of
these
interventions
in
clinical
practice
(a
minimally
important
difference)
remains
unclear.
We
aimed
determine
this
with
anchor‐based
methods.
Methods
This
was
a
post
hoc
analysis
three
studies
investigating
pain
management
after
hip
or
knee
arthroplasty
(PANSAID
[NCT02571361],
DEX‐2‐TKA
[NCT03506789]
and
Pain
Map
[NCT02340052]).
overall
population
median
aged
70,
ASA
2,
54%
female.
examined
correlation
between
0
24
h
postoperative
iv
morphine
equivalent
consumption
severity
nausea,
vomiting,
sedation
dizziness.
anchor
different
degrees
opioid‐related
adverse
events.
primary
outcome
difference
patients
experiencing
no
versus
only
mild
Secondary
outcomes
included
moderate
severe
Hodges–Lehmann
differences,
Wilcoxon–Mann–Whitney
tests
quantile
regression.
Results
6
mg
(95%
confidence
interval:
4–8)
events,
5
(2–8)
events
(−4
4)
Conclusions
In
populations
comparable
post‐hoc
(orthopaedic
surgery,
age
70
2),
we
suggest
for
0–24
consumption.
BMC Anesthesiology,
Journal Year:
2024,
Volume and Issue:
24(1)
Published: Feb. 1, 2024
Abstract
Background
Esketamine,
recognized
for
its
analgesic,
sedative,
and
anti-inflammatory
qualities,
is
integral
in
multimodal
analgesia.
However,
the
potential
opioid-sparing
effects
of
intravenous
esketamine,
along
with
impact
on
inflammatory
responses,
cognitive
function
during
laparoscopic
surgery,
remain
unexplored.
Methods
In
this
study,
90
patients
scheduled
cholecystectomy
were
equally
randomized
into
three
groups:
a
normal
saline
control
group
(NS),
low-dose
esketamine
(LS)
high-dose
(HS).
Subsequently,
we
monitored
several
parameters:
hemodynamics,
levels
stress
intraoperative
doses
sufentanil,
remifentanil,
propofol,
24-hour
postoperative
sufentanil
requirements.
We
also
evaluated
alterations
function,
perioperative
indicators,
adverse
reactions
among
groups.
Results
Compared
to
their
5
minutes
prior
anesthesia
(T
0
)
30
post-operation
4
),
NS
exhibited
more
significant
decrease
Mean
Arterial
Pressure
(MAP)
Heart
Rate
(HR)
at
various
time
intervals:
after
skin
incision
1
post-incision
2
conclusion
operation
3
compared
LS
HS
groups(
P
<
0.05).
Furthermore,
greater
increase
adrenaline
(AD),
noradrenaline
(NE),
endothelin
(ET),
C-reactive
protein
(CRP),
tumor
necrosis
factor-alpha
(TNF-α),
interleukin-6
(IL-6)
T
,
so
than
other
two
24
hours
had
significantly
higher
Montreal
Cognitive
Assessment
(MoCA)
scores
those
group(
The
groups
required
lower
surgery
(
0.05),
experienced
shorter
recovery
times,
incidences
nausea,
vomiting,
respiratory
depression
Conclusion
administration
has
been
shown
be
safe,
effective,
dependable
context
gallbladder
surgery.
It
capacity
stabilize
hemodynamic
ameliorate
both
from
hastens
recovery.
it
fosters
restoration
function.
Notably,
when
combined
nalbuphine,
exhibits
effects,
reducing
outcomes.
Trial
registration
trial
registered
China
Clinical
Trials
Registry
Registration
Number:
ChiCTR2300067596.
Retrospectively
(date
registration:
12/01/2023).
The Journal of Clinical Pharmacology,
Journal Year:
2021,
Volume and Issue:
61(S2)
Published: Aug. 1, 2021
Abstract
Opioids
were
the
most
common
drug
class
resulting
in
overdose
deaths
United
States
2019.
Widespread
clinical
use
of
prescription
opioids
for
moderate
to
severe
pain
contributed
ongoing
opioid
epidemic
with
subsequent
emergence
fentanyl‐laced
heroin.
More
potent
analogues
fentanyl
and
structurally
diverse
receptor
agonists
such
as
AH‐7921
MT‐45
are
fueling
an
increasingly
illicit
supply.
Overdose
from
synthetic
high
binding
affinities
may
not
respond
a
typical
naloxone
dose,
thereby
rendering
autoinjectors
less
effective,
requiring
higher
antagonist
doses
or
confusing
picture
health
care
providers.
Nonscheduled
drugs
loperamide
dextromethorphan
associated
dependence
risk
easier
access
makes
them
attractive
users.
Despite
opioid‐mediated
pathway,
several
present
unique
pharmacodynamic
properties
leading
acute
toxicity
development.
Pharmacokinetic
considerations
involve
half‐life
parent
its
metabolites
well
toxicity,
is
established
tramadol,
codeine,
oxycodone.
considerations,
toxicities,
treatment
approaches
notable
reviewed.
Pharmacological Reviews,
Journal Year:
2023,
Volume and Issue:
75(6), P. 1062 - 1118
Published: June 15, 2023
Oxycodone,
a
semisynthetic
derivative
of
naturally
occurring
thebaine,
an
opioid
alkaloid,
has
been
available
for
more
than
100
years.
Although
thebaine
cannot
be
used
therapeutically
due
to
the
occurrence
convulsions
at
higher
doses,
it
converted
number
other
widely
compounds
that
include
naloxone,
naltrexone,
buprenorphine,
and
oxycodone.
Despite
early
identification
oxycodone,
was
not
until
1990s
clinical
studies
began
explore
its
analgesic
efficacy.
These
were
followed
by
pursuit
several
preclinical
examine
effects
abuse
liability
oxycodone
in
laboratory
animals
subjective
human
volunteers.
For
years
forefront
crisis,
playing
significant
role
contributing
misuse
abuse,
with
suggestions
led
transitioning
opioids.
Several
concerns
expressed
as
1940s
had
potential
similar
heroin
morphine.
Both
animal
have
confirmed,
some
cases
amplified,
these
warnings.
sharing
structure
morphine
pharmacological
actions
also
mediated
μ-opioid
receptor,
there
are
differences
pharmacology
neurobiology
The
data
emerged
from
many
efforts
analyze
molecular
mechanism
generated
considerable
insight
into
actions,
reviewed
here,
which,
turn,
provided
new
information
on
receptor
pharmacology.
SIGNIFICANCE
STATEMENT:
agonist,
synthesized
1916
introduced
use
Germany
1917.
It
studied
extensively
therapeutic
acute
chronic
neuropathic
pain
alternative
Oxycodone
drug
widespread
abuse.
This
article
brings
together
integrated,
detailed
review
recent
advances
identify
analgesics
without
liability.
Journal of Neuroscience,
Journal Year:
2022,
Volume and Issue:
43(2), P. 308 - 318
Published: Nov. 17, 2022
Opioid
exposure
and
withdrawal
both
cause
adaptations
in
brain
circuits
that
may
contribute
to
abuse
liability.
These
vary
magnitude
direction
following
different
patterns
of
opioid
exposure,
but
few
studies
have
systematically
manipulated
the
pattern
administration
while
measuring
neurobiological
impact.
In
this
study,
we
compared
cellular
synaptic
nucleus
accumbens
shell
caused
by
morphine
was
either
continuous
or
interrupted
daily
bouts
naloxone-precipitated
withdrawal.
At
behavioral
level,
psychomotor
tolerance,
which
reversed
when
continuity
action
Using
ex
vivo
slice
electrophysiology
female
male
mice,
investigated
how
these
altered
intrinsic
excitability
plasticity
medium
spiny
neurons
(MSNs)
expressing
D1
D2
dopamine
receptor.
We
found
morphine-evoked
at
excitatory
synapses
were
predominately
conserved
between
administration,
there
divergent
effects
on
inhibitory
subsequent
balance
input.
Overall,
our
data
suggest
produces
dampen
output
D1-MSNs,
are
canonically
thought
promote
reward-related
behaviors.
Interruption
otherwise
does
not
D1-MSN
functional
same
extent,
enhance
responses
exposure.
Our
findings
support
hypothesis
maintaining
could
be
an
effective
therapeutic
strategy
minimize
vulnerability
use
disorders.
SIGNIFICANCE
STATEMENT
Withdrawal
plays
a
key
role
cycle
addiction
opioids
like
morphine.
studied
repeated
cycles
from
can
change
function
accumbens,
is
important
region
for
reward
addiction.
Different
unique
changes
communication
nature
depended
type
neuron
being
studied.
The
specific
increase
This
highlights
importance
reducing
preventing
experience
during
treatment.
The International Journal of Neuropsychopharmacology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 20, 2025
Abstract
Opioid
use
disorder
(OUD)
affects
over
40
million
people
worldwide,
creating
significant
social
and
economic
burdens.
Medication
for
opioid
(MOUD)
is
often
considered
the
primary
treatment
approach
OUD.
MOUD,
including
methadone,
buprenorphine,
naltrexone
effective
some,
but
its
benefits
may
be
limited
by
poor
adherence
to
recommendations.
Immunopharmacotherapy
offers
an
innovative
using
vaccines
generate
antibodies
that
neutralize
opioids,
blocking
them
from
crossing
blood-brain
barrier
reducing
their
psychoactive
effects.
To
date,
only
three
clinical
trials
have
been
published.
While
these
studies
demonstrated
potential
of
relapse
prevention,
there
currently
no
standardized
protocol
evaluating
effectiveness.
We
reviewed
recent
preclinical
efficacy
targeting
heroin,
morphine,
oxycodone,
hydrocodone,
fentanyl.
These
showed
against
opioids
reduced
drug
reinforcement,
decreased
opioid-induced
antinociception,
increased
survival
rates
lethal
doses.
also
importance
vaccine
formulation
adjuvants
in
enhancing
antibody
production
specificity.
Finally,
we
highlighted
strengths
concerns
associated
with
treatment,
ethical
considerations.
