ACS Medicinal Chemistry Letters,
Год журнала:
2022,
Номер
13(7), С. 1052 - 1061
Опубликована: Июнь 21, 2022
Overactive
bladder
(OAB)
is
a
syndrome
causing
sudden
and
unstoppable
need
to
urinate
with
significant
global
prevalence.
Several
drugs
are
used
treat
OAB;
however,
they
have
various
side
effects.
Therefore,
new
treatment
options
for
OAB
required.
A
series
of
novel
5-oxo-N-phenyl-1-thioxo-4,5-dihydro-1H-thiazolo[3,4-a]quinazoline-3-carboxamide
derivatives
were
synthesized
evaluated
their
large-conductance
voltage-
Ca2+-activated
K+
channel
activation
through
cell-based
fluorescence
assay
electrophysiological
recordings.
compounds,
including
7-bromo
substituent
on
the
heterocyclic
system,
showed
increased
currents.
Among
derivatives,
compound
12h
exhibited
potent
in
vitro
activity
half-maximal
effective
concentration
(EC50)
2.89
μM,
good
oral
pharmacokinetic
properties
(area
under
curve
half-life),
vivo
efficacy
spontaneously
hypertensive
rat
model.
Neurourology and Urodynamics,
Год журнала:
2022,
Номер
41(8), С. 1928 - 1933
Опубликована: Сен. 6, 2022
Anticholinergic
medications
are
widely
used
in
the
treatment
of
overactive
bladder
(OAB),
as
well
for
short-term
symptoms
following
a
variety
urologic
surgeries.
Mounting
evidence
points
to
an
association
between
anticholinergic
and
increased
risk
incident
dementia.
The
Society
Urodynamics,
Female
Pelvic
Medicine,
Urogenital
Reconstruction
(SUFU)
thus
convened
committee
subject
experts
contextualize
current
understanding
cognitive
risks
patient
population
provide
practical
clinical
guidance
on
this
subject.Statements
based
expert
literature
review
committee's
opinion.
document
has
been
reviewed
approved
by
SUFU
board.Chronic
use
(>3
months)
OAB
is
likely
associated
with
new-onset
Short-term
(<4
weeks)
most
safe
individuals.
Clinicians
should
consider
potential
all
populations
when
prescribing
anticholinergics
chronic
use.
Consideration
be
given
progressing
advanced
therapy
(botulinum
toxin
or
neuromodulation)
earlier
paradigm
CONCLUSIONS:
body
supports
small
but
significant
dementia
exposure
medications.
Potential
harms
balanced
against
quality
life
improvement
treatment.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 13, 2025
The
BKCa
channel,
a
large-conductance
calcium-activated
potassium
plays
crucial
role
in
maintaining
the
homeostasis
of
micturition
cycle
and
airway-related
functions.
In
this
study,
we
optimized
novel
channel
activator,
4d,
with
diphenyl
ether
structure
identified
from
library
screening.
This
led
to
discovery
potent
activators,
10b
(EC50
=
0.12
μM,
cell-based
assay)
51b,
an
orally
bioavailable
derivative.
Compound
demonstrated
vivo
efficacy
spontaneous
hypertensive
rat
(SHR)
urinary
incontinence
model,
while
compound
51b
showed
dose-dependent
cough
suppression
ED50
11.8
mg/kg
citric
acid-induced
model.
Furthermore,
reported
cryo-electron
microscopy
(cryo-EM)
structures
complex
at
resolutions
2.8
3.4
Å.
Based
on
structural
analyses,
determined
binding
sites
key
interaction
residues
which
were
validated
via
mutation
studies.
European Journal of Neurology,
Год журнала:
2025,
Номер
32(4)
Опубликована: Апрель 1, 2025
ABSTRACT
Background
Urinary
and
sexual
symptoms
are
common
following
neurological
disease,
we
aimed
to
develop
multidisciplinary
inter‐society
evidence‐based
management
guidelines.
Methods
The
ADAPTE
framework
was
used,
a
systematic
search
of
guidelines
published
in
different
languages
performed.
Guidelines,
consensus
statements,
reviews
were
included,
guideline
quality
appraised
using
AGREE
II.
Patient
representatives
reviewed
the
relevance
suitability
recommendations.
A
modified
Delphi
process
integrating
Evidence
Decision
adapted
from
GRADE
Oxford
Centre
for
Based
Medicine
system
used
reach
on
recommendation
wording
strength.
Results
Recommendations
drafted,
guidelines/consensus
statements
(59
urinary,
50
sexual),
(8
2
sexual)
others
(7
urinary,13
wordings/strengths
achieved
at
least
80%
through
rounds.
Eleven
recommendations,
19
good
practice
8
consensus‐based
recommendations
made.
Individuals
with
diseases
should
be
asked
about
urogenital
undergo
targeted
physical
examination
when
appropriate.
symptom
assessments
include
urinalysis,
bladder
diary
completion,
post‐void
residual
volume
measurement.
Treatments
fluid
intake
optimization,
pelvic
physiotherapy,
tibial
nerve
stimulation,
oral
medications.
retention
is
managed
by
intermittent
catheterization.
Antibiotics
not
recommended
treat
asymptomatic
bacteriuria.
Suprapubic
catheterization
preferred
long‐term
comprehensive
history
taken,
focusing
multidimensional
factors
affecting
health.
lubricants,
vibrators,
phosphodiesterase‐5
inhibitors.
Red
flag
warrant
shared‐care
approach
specialist
colleagues.
Conclusions
38
NEUROGED
will
guide
neurologists
comprehensively
manage
reported
individuals
diseases.
Urogynecology,
Год журнала:
2022,
Номер
29(1S), С. S1 - S19
Опубликована: Окт. 22, 2022
Importance
Overactive
bladder
(OAB)
is
prevalent
in
older
adults
whom
management
complicated
by
comorbidities
and
greater
vulnerability
to
the
cognitive
effects
of
antimuscarinic
medications.
Objectives
The
aim
this
study
provide
a
comprehensive
evidence-based
summary
2021
State-of-the-Science
(SOS)
conference
multidisciplinary
expert
literature
review
on
OAB
impairment.
Study
Design
American
Urogynecologic
Society
Pelvic
Floor
Disorders
Research
Foundation
convened
3-day
collaborative
conference.
Experts
from
fields
examined
function,
higher
neural
control
patient,
risk
factors
for
impairment
patients,
medications
treatment,
phenotyping,
conservative
advanced
therapies,
need
approach
person-centered
treatment.
Translational
topics
included
blood-brain
barrier,
purine
metabolome,
mechanotransduction,
gene
therapy
targets.
Results
surrounding
treatment
efficacy
cognitively
impaired
individuals
limited.
Short-
long-term
outcomes
regarding
cognition
are
mixed;
however,
anticholinergic
burden
duration
use
influence
risk.
Oxybutynin
most
consistently
associated
with
negative
short-term,
prospective
studies.
Although
data
limited,
beta-adrenergic
agonists
do
not
appear
confer
same
Conclusions
SOS
report
provides
fundamental,
translational,
clinical
research
emphasis
risks
Duration
type,
specifically
oxybutynin
when
examining
treatments,
appears
have
impact;
conclusions
limited
primarily
intact
population
studied.
Given
current
evidence,
it
prudent
minimize
emphasizing
nonantimuscarinic
therapeutic
regimens
and/or
those
Indian Journal of Urology,
Год журнала:
2024,
Номер
40(2), С. 82 - 87
Опубликована: Апрель 1, 2024
This
narrative
review
discusses
the
relationship
between
anticholinergic
medications
and
cognitive
change
specifically
in
patients
with
neurogenic
lower
urinary
tract
dysfunction
(NLUTD).
NLUTD
is
prevalent
various
conditions,
including
spinal
cord
injury
(SCI),
spina
bifida
(SB),
multiple
sclerosis
(MS),
Parkinson's,
stroke,
dementia
often
requires
overactive
bladder
(OAB)
medications.
In
general
population,
among
those
OAB,
several
studies
have
found
a
significant
association
this
class
of
side
effects,
mostly
when
used
for
>
90
days.
These
effects
may
be
particularly
relevant
to
people
due
their
higher
baseline
risk
impairment.
Two
(one
SCI
another
MS)
evidence
impairment
use
OAB
anticholinergics
(specifically
oxybutynin
tolterodine).
People
commonly
anticholinergics,
there
that
tolterodine
impair
cognition
population.
recent
children
SB
studied
12
months
solifenacin
6
fesoterodine/oxybutynin
was
no
neuropsychological
testing.
Clinical
Parkinson's
disease
prior
stroke
not
shown
trospium,
darifenacin,
or
fesoterodine
impact
on
measures.
summary,
pose
than
newer
NLUTD;
experience
anticholinergics.
Further
study
necessary
confirm
safety,
as
population
high
exposure
Advocating
potentially
safer
if
concern
about
risks.
