Sigma-1 receptor as an emerging target for painful diabetic neuropathy—a review
Exploration of neuroscience,
Journal Year:
2025,
Volume and Issue:
4
Published: April 1, 2025
Neuropathic
pain
(NP)
is
a
significant
global
health
challenge,
affecting
an
estimated
7–10%
of
the
population.
Painful
diabetic
neuropathy
(PDN),
severe
complication
diabetes,
impacts
approximately
one
in
every
three
patients.
With
rising
prevalence
PDN
projected
to
become
increasingly
urgent
concern.
Current
treatments
for
often
provide
inadequate
relief
and
are
associated
with
adverse
side
effects,
emphasizing
need
safe
effective
therapeutic
options.
This
review
examines
limitations
existing
pharmacological
therapies
presents
sigma-1
receptor
(S1R)
as
promising
target.
We
explore
biological
role
S1R,
its
implication
NP
PDN,
structural
biology,
expanding
preclinical
clinical
evidence
supporting
potential.
Furthermore,
we
present
various
S1R
antagonists
addressing
particular
focus
on
E-52862
[18F]FTC-146.
These
compounds
represent
first-in-class
ligands
diagnostic
applications,
respectively,
marking
advances
development
antagonists.
underscores
potential
antagonism
strategy
developing
more
ability
significantly
improve
patient
outcomes.
Language: Английский
E‐52862—A selective sigma‐1 receptor antagonist, in peripheral neuropathic pain: Two randomized, double‐blind, phase 2 studies in patients with chronic postsurgical pain and painful diabetic neuropathy
European Journal of Pain,
Journal Year:
2024,
Volume and Issue:
29(1)
Published: Dec. 4, 2024
Abstract
Background
We
report
the
efficacy
and
safety
of
E‐52862—a
selective,
sigma‐1
receptor
antagonist—from
phase
2,
randomized,
proof‐of‐concept
studies
in
patients
with
moderate‐to‐severe,
neuropathic,
chronic
postsurgical
pain
(CPSP)
painful
diabetic
neuropathy
(PDN).
Methods
Adult
(CPSP
[
N
=
116];
PDN
163])
were
randomized
at
a
1:1
ratio
to
4
weeks
treatment
E‐52862
n
55];
85])
or
placebo
61];
78])
orally
once
daily.
Pain
intensity
scores
measured
using
numerical
rating
scale
from
0
(no
pain)
10
(worst
imaginable).
The
primary
analysis
population
comprised
who
received
study
drug
≥1
baseline
on‐treatment
observation
(full
set).
Results
In
CPSP,
mean
average
was
6.2
for
vs.
6.5
placebo.
Week
change
(CFB)
−1.6
–0.9
(least
squares
difference
[LSMD]:
−0.9;
p
0.029).
PDN,
5.3
5.4
CFB
−2.2
–2.1
(LSMD:
–0.1;
0.766).
Treatment‐emergent
adverse
events
(TEAEs)
reported
90.9%
E‐52862‐treated
76.7%
placebo‐treated
CPSP
34.1%
26.9%
PDN.
Serious
TEAEs
occurred
only:
E‐52862:
5.5%;
placebo:
6.7%.
Conclusions
demonstrated
superior
relief
after
weeks.
Reductions
seen
E‐52862;
high
response
rates
may
have
prevented
differentiation
between
treatments.
had
acceptable
tolerability
both
populations.
Significance
Statement
These
validate
mode
action
E‐52862,
selective
antagonist.
resulted
clinically
meaningful
relief.
reductions
findings
are
relevant
given
that
neuropathic
is
highly
incapacitating,
lacking
effective
treatments
representing
significant
unmet
medical
need,
support
further
development
antagonists
peripheral
pain.
Language: Английский
Ligand docking in the sigma-1 receptor compared to the sigma-1 receptor-BiP complex and the effects of agonists and antagonists on C. elegans lifespans
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
182, P. 117783 - 117783
Published: Dec. 26, 2024
Language: Английский