Tohoku J. exp. Med., 1976, 120, 197-198 Short
Effect
of Dibutyryl
Transmission
Cyclic
in
AMP
Myasthenia
on
Report
Neuromuscular
Gravis
YASUHIKO HASHIMOTO, HISAKOSASAKIand KENICHIIWATSUKI Department of Anesthesiology,Tohoku University School of Medicine, Sendai
HASHIMOTO, an
Y.,
Neuromuscular
1976,
120
(D-c
(2),
AMP)
the
study
and
and
of
suggests
The
effect
that
of
transient
D-cAMP
has
studied
caused
decrease
an
cyclic
in
a
in
effect
a
in
patient
with in
my single
resulted
finding
of
patients
neuromuscular
Med.,
increase which
The
AMP
exp.
monophosphate
slight
tension
D-cAMP.
anti-fatigue
AMP;
Cyclic J.
3•Œ,5•Œ-cyclic
was
after
of Dibutyryl Tohoku
dibutyryl
D-cAMP
disappeared
gravis.•\dibutyryl
Effect Gravis.
transmission
initial
stimuli
K.
Myasthenia
anesthesia.
an
2 Hz
IWATSURI,
in
-
during
tension, trains
H.
neuromuscular
gravis
twitch the
197-198
on
asthenia
SASAKI, transmission
from
the
with
present
myasthenia
transmission;
myasthenia
gravis
Epinephrine release
of
is
epinephrine
stimulates
activating at
the
nerve
in
nerve
Ambenonium
was
anesthesia
the
Kohden
the
1967). to
facilitating
been
Based
on
anesthesia
xanthines,
twitch
in
a
by
acetylcholine
tension
these
on
that
(cAMP) of
Furthermore, the
the
suggested
release
increase
1973).
by has
monophosphate
augments
(D-cAMP)
through
the 10
male.
day
sec. a
as
regular
with nerve
stimulator
of
the
intercostal
findings,
the
response
elicited
patient
was
with
effect by
myasthenia
to
morning
transducer
illness
the
operation,
induction
dose.
at
Trains
of
adduction
attached
to
a
he
was
the
stimuli
of
the
induced
elbow
using
of 2
Hz
middle
recorder
was
(0.5-1.5%).
stimuli
of
of
anesthesia.
halothane
indirectly
6
10mg
of
Anesthesia and
square-wave
to
appeared with
the
oxygen
electrodes. due
his
treatment Before
prior
stimulated
tension
force-displacement
ago. hr
supramaximal
needle
resultant
of
medical
nitrous-oxide
with
subcutaneous
months one
a
symptom
The
six
given
median
first
atropine
maintained
The
The
weakness.
started and
also
SEN-1101
multipurpose
a
0.2
msec
were
also
finger
(Nihon
was
Kohden
polygraph).
When
a steady
facilitation
in in
tension of
and
Received
twitch
tension
administration control
a
and
using
al.
during
muscular
meperidine
10mg
recorded
studied
31-year-old
thiamylal
for
change
a
times
with
delivered
reported
monophosphate
was
generalized
three
During
Malschinski
been et
It
3•Œ,5•Œ-cyclic thus
and
(Jacobs
transmission
terminals.
thymectomy.
a
sodium
neuromuscular
nucleotide
have
stimulation
premedicated
duration
adenosine
the
3•Œ,5•Œ-cyclic
was
as
ambenonium
Nihon
of
formation
patients
patient
ago
with
nerve
and
adenosine
undergoing
years
mortor
hydrolysis,
myasthenic
peripheral
The
improve
the
(Breckenridge
cAMP
dibutyryl
gravis
to
from
cyclase
terminals of
muscle
known
the
adenyl
inhibitors
of
well
acetylcholine
an
response
was
observed
did
not
occur
300
mg
of
initial
transient
for publication,
was by in
normal
D-cAMP,
trains
an of
initial stimuli
subjects. an
decrease
June
obtained, the
increase in
tension
25, 1976 197
Around in
single which
transient (Fig. 10
decrease 1,
min
upper after
twitch
tension
resulted
from
followed trace). the by the
by
Such
a
intravenous 23% trains
to
the of
2
198
Y. Hashimoto
Fig.
1. A continuous twitch responses.
tracing
of the effect
et al.
of D-cAMP
on single
and
repetitive
Hz stimuli disappeared (Fig. 1, middle trace). An increase in single twitch tension sustained 20 min after the administration of D-cAMP, but an initial transient decrease became noted again (Fig. 1, middle and lower traces). Goldberg and Singer (1969) reported that D-cAMP increases the amplitude of end plate potential in the isolated rat diaphragm. The present study demonstrated that DcAMP caused a slight increase in twitch tension and an "anti-fatigue" effect in a patient with myasthenia gravis, probably owing to its certain effect on the mortor nerve terminals. The augmentation of twitch tension, however, may also reflect the effect of D-cAMP on postsynaptic events and muscle blood flow. Further clinical studies are necessary to evaluate the efficacy of D-cAMP in the treatment of myasthenia gravis including the mechanism of its action. References
1) Breckenridge, B.M. & Malschinski, F.M. (1967) Theophylline, epinephrine, and neostigmine facilitation of neuromuscular transmission. Proc. nat. Acad. Sci. USA, 57, 1893-1897. 2) Goldberg, A.L. & Singer, J.J. (1969) Evidence for a role of cyclic AMP in neuromus cular transmission. Proc. nat. Acad. Sci. USA, 64, 134-141. 3) Jacbos, R., Karczmar, A.G. & Brumlid, J. (1973) Theophylline compounds and myasthenia gravis. 1. In vitro studies. Clin. Pharmacol. Ther., 14, 374-379.
Effect
of Dibutyryl
Transmission
Cyclic
in
AMP
Myasthenia
on
Report
Neuromuscular
Gravis
YASUHIKO HASHIMOTO, HISAKOSASAKIand KENICHIIWATSUKI Department of Anesthesiology,Tohoku University School of Medicine, Sendai
HASHIMOTO, an
Y.,
Neuromuscular
1976,
120
(D-c
(2),
AMP)
the
study
and
and
of
suggests
The
effect
that
of
transient
D-cAMP
has
studied
caused
decrease
an
cyclic
in
a
in
effect
a
in
patient
with in
my single
resulted
finding
of
patients
neuromuscular
Med.,
increase which
The
AMP
exp.
monophosphate
slight
tension
D-cAMP.
anti-fatigue
AMP;
Cyclic J.
3•Œ,5•Œ-cyclic
was
after
of Dibutyryl Tohoku
dibutyryl
D-cAMP
disappeared
gravis.•\dibutyryl
Effect Gravis.
transmission
initial
stimuli
K.
Myasthenia
anesthesia.
an
2 Hz
IWATSURI,
in
-
during
tension, trains
H.
neuromuscular
gravis
twitch the
197-198
on
asthenia
SASAKI, transmission
from
the
with
present
myasthenia
transmission;
myasthenia
gravis
Epinephrine release
of
is
epinephrine
stimulates
activating at
the
nerve
in
nerve
Ambenonium
was
anesthesia
the
Kohden
the
1967). to
facilitating
been
Based
on
anesthesia
xanthines,
twitch
in
a
by
acetylcholine
tension
these
on
that
(cAMP) of
Furthermore, the
the
suggested
release
increase
1973).
by has
monophosphate
augments
(D-cAMP)
through
the 10
male.
day
sec. a
as
regular
with nerve
stimulator
of
the
intercostal
findings,
the
response
elicited
patient
was
with
effect by
myasthenia
to
morning
transducer
illness
the
operation,
induction
dose.
at
Trains
of
adduction
attached
to
a
he
was
the
stimuli
of
the
induced
elbow
using
of 2
Hz
middle
recorder
was
(0.5-1.5%).
stimuli
of
of
anesthesia.
halothane
indirectly
6
10mg
of
Anesthesia and
square-wave
to
appeared with
the
oxygen
electrodes. due
his
treatment Before
prior
stimulated
tension
force-displacement
ago. hr
supramaximal
needle
resultant
of
medical
nitrous-oxide
with
subcutaneous
months one
a
symptom
The
six
given
median
first
atropine
maintained
The
The
weakness.
started and
also
SEN-1101
multipurpose
a
0.2
msec
were
also
finger
(Nihon
was
Kohden
polygraph).
When
a steady
facilitation
in in
tension of
and
Received
twitch
tension
administration control
a
and
using
al.
during
muscular
meperidine
10mg
recorded
studied
31-year-old
thiamylal
for
change
a
times
with
delivered
reported
monophosphate
was
generalized
three
During
Malschinski
been et
It
3•Œ,5•Œ-cyclic thus
and
(Jacobs
transmission
terminals.
thymectomy.
a
sodium
neuromuscular
nucleotide
have
stimulation
premedicated
duration
adenosine
the
3•Œ,5•Œ-cyclic
was
as
ambenonium
Nihon
of
formation
patients
patient
ago
with
nerve
and
adenosine
undergoing
years
mortor
hydrolysis,
myasthenic
peripheral
The
improve
the
(Breckenridge
cAMP
dibutyryl
gravis
to
from
cyclase
terminals of
muscle
known
the
adenyl
inhibitors
of
well
acetylcholine
an
response
was
observed
did
not
occur
300
mg
of
initial
transient
for publication,
was by in
normal
D-cAMP,
trains
an of
initial stimuli
subjects. an
decrease
June
obtained, the
increase in
tension
25, 1976 197
Around in
single which
transient (Fig. 10
decrease 1,
min
upper after
twitch
tension
resulted
from
followed trace). the by the
by
Such
a
intravenous 23% trains
to
the of
2
198
Y. Hashimoto
Fig.
1. A continuous twitch responses.
tracing
of the effect
et al.
of D-cAMP
on single
and
repetitive
Hz stimuli disappeared (Fig. 1, middle trace). An increase in single twitch tension sustained 20 min after the administration of D-cAMP, but an initial transient decrease became noted again (Fig. 1, middle and lower traces). Goldberg and Singer (1969) reported that D-cAMP increases the amplitude of end plate potential in the isolated rat diaphragm. The present study demonstrated that DcAMP caused a slight increase in twitch tension and an "anti-fatigue" effect in a patient with myasthenia gravis, probably owing to its certain effect on the mortor nerve terminals. The augmentation of twitch tension, however, may also reflect the effect of D-cAMP on postsynaptic events and muscle blood flow. Further clinical studies are necessary to evaluate the efficacy of D-cAMP in the treatment of myasthenia gravis including the mechanism of its action. References
1) Breckenridge, B.M. & Malschinski, F.M. (1967) Theophylline, epinephrine, and neostigmine facilitation of neuromuscular transmission. Proc. nat. Acad. Sci. USA, 57, 1893-1897. 2) Goldberg, A.L. & Singer, J.J. (1969) Evidence for a role of cyclic AMP in neuromus cular transmission. Proc. nat. Acad. Sci. USA, 64, 134-141. 3) Jacbos, R., Karczmar, A.G. & Brumlid, J. (1973) Theophylline compounds and myasthenia gravis. 1. In vitro studies. Clin. Pharmacol. Ther., 14, 374-379.
