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Pharmacology of B-GYKI-38 233 a new antiarrhythmic agent
Pharmaco~gicalResea~hCommunica~n¢VoL2~Supp/ementL1988
71
PHARMACOLOGY OF B-GYKI-38 233 A N E W A N T I A R R H Y T H M I C A G E N T GySrgy Rabloczky, AndrAs Varr6, M~ria KGrthy, Ilona B6dl,Andrea Jedn~kovits, L~szl6 Szathm~ry, L~szl6 Jaszlits, Ildik6 Kir~ly Institute for Drug Research, 1325 Budapest, P.O.Box 82. Hungary Key words: antiarrhythmic - cardiovascular actions - central side effects All of the recently developed
antiarrhythmic agents
proved
to be strongly acting against a series of experimental ventri~ular arrhythmias.
In patients they produced favorable thera-
peutic effects, too. However almost all of them were unable to abolish the greatest danger of sudden
cardiac death.
advantageous
in cardiac patient, The further search
antiarrhythmic compounds
ratio has been considered worthwhile
i.e. the risk
for newer more
of better risk/benefit by several authors.
In the cardiovascular laboratory of Institute for Drug Research & new aminoguanidine derivative /1-/2,6-dimetyl-phenylamino]-3,3-dimethyl guanidine,hydrochloride;B-GYKI-38 be highly active /K~rthy et al. 1985; After i.p. and
233/ seemed to
Varr6 et ai, 1987/.
oral administration
B-GYKI-38 233
produced
the lowest EDso value, the best ratio of LDSo/EDso in aconitine mice in comparison with lidocaine, quinidin@ or amiodarone. It increased the fibrillation threshold in cats more
strongly
than mexiletine or quinidine did. It could effectively antagonize
the ouabain
early phase
induced arrhythmia in
of postinfarction
guinea pigs.
In the
arrhythmias after coronary liga-
tion B-GYKI-38 233 could decrease the occurence of
ventricular
fibrillations and thereby it highly increased the
survival rate
0031-6989/88/20S10071-2/$03.00J0
@ 1988 The Italian Pharmacological Society
Pharmaco~gicalResearchCommunmation~Vo~2~ SupplementL1988
72
of the conscious rats. overstimulation
Ventricular fibrillation
and local epicardial cooling were
anaesthetized dogs
by that new compound.
Class I antiarrhythmic drugs inotropic,
provoked
it caused a
In
blocked in
contrast
transient
with
positive
coronary blood flow increasing and antianginal ef-
fects, as well;
did not antagonize the electroconvulsions,
anticonVulsant
activity was weaker
In intracellular cardiac B-GYKI-38
by
than that of
mexiletine.
electrophysiological
experiments
233 depressed the upstroke velocity
dependent manner,
in a
reduced the amplitude of action
frequency potential,
shortened repolarization and effective refractory period, did not change
its
but
resting potential in the canine Purkinje fiber.
At a cycle length of 400 ms
it could lengthen
repolarization
and depress Vma x, while resting potential and action potential amplitude was unchanged
in dog ventricular muscle
has no cardiovascular or behavioural cats. B-GYKI-38
fiber.
It
side-effects in conscious
233 proved to be a very active
antiarrhythmic
compound which possessed both Class I c and Class III properties according to our investigations.
REFERENCES
KUrthy M., G. Rabloczky, A. Varr6, L. Szathm~ry, L. Jaszlits J. Wellmann, I. ~rczi; Advances Pharmacol. Res. and Practice. Proc. 4th Congr. of Hung. Pharmacol. Soc. Vol. I: Sec. 2. Pharmacol of the vascular system, 211-215, 1985. Varr6 A., G. Rabloczky, M. KHrthy, L. Jaszlits, I. ~rczi; Abstracts of Xth Congr. IUPHAR, Sydney, Australia, PI4D76, 1987.
71
PHARMACOLOGY OF B-GYKI-38 233 A N E W A N T I A R R H Y T H M I C A G E N T GySrgy Rabloczky, AndrAs Varr6, M~ria KGrthy, Ilona B6dl,Andrea Jedn~kovits, L~szl6 Szathm~ry, L~szl6 Jaszlits, Ildik6 Kir~ly Institute for Drug Research, 1325 Budapest, P.O.Box 82. Hungary Key words: antiarrhythmic - cardiovascular actions - central side effects All of the recently developed
antiarrhythmic agents
proved
to be strongly acting against a series of experimental ventri~ular arrhythmias.
In patients they produced favorable thera-
peutic effects, too. However almost all of them were unable to abolish the greatest danger of sudden
cardiac death.
advantageous
in cardiac patient, The further search
antiarrhythmic compounds
ratio has been considered worthwhile
i.e. the risk
for newer more
of better risk/benefit by several authors.
In the cardiovascular laboratory of Institute for Drug Research & new aminoguanidine derivative /1-/2,6-dimetyl-phenylamino]-3,3-dimethyl guanidine,hydrochloride;B-GYKI-38 be highly active /K~rthy et al. 1985; After i.p. and
233/ seemed to
Varr6 et ai, 1987/.
oral administration
B-GYKI-38 233
produced
the lowest EDso value, the best ratio of LDSo/EDso in aconitine mice in comparison with lidocaine, quinidin@ or amiodarone. It increased the fibrillation threshold in cats more
strongly
than mexiletine or quinidine did. It could effectively antagonize
the ouabain
early phase
induced arrhythmia in
of postinfarction
guinea pigs.
In the
arrhythmias after coronary liga-
tion B-GYKI-38 233 could decrease the occurence of
ventricular
fibrillations and thereby it highly increased the
survival rate
0031-6989/88/20S10071-2/$03.00J0
@ 1988 The Italian Pharmacological Society
Pharmaco~gicalResearchCommunmation~Vo~2~ SupplementL1988
72
of the conscious rats. overstimulation
Ventricular fibrillation
and local epicardial cooling were
anaesthetized dogs
by that new compound.
Class I antiarrhythmic drugs inotropic,
provoked
it caused a
In
blocked in
contrast
transient
with
positive
coronary blood flow increasing and antianginal ef-
fects, as well;
did not antagonize the electroconvulsions,
anticonVulsant
activity was weaker
In intracellular cardiac B-GYKI-38
by
than that of
mexiletine.
electrophysiological
experiments
233 depressed the upstroke velocity
dependent manner,
in a
reduced the amplitude of action
frequency potential,
shortened repolarization and effective refractory period, did not change
its
but
resting potential in the canine Purkinje fiber.
At a cycle length of 400 ms
it could lengthen
repolarization
and depress Vma x, while resting potential and action potential amplitude was unchanged
in dog ventricular muscle
has no cardiovascular or behavioural cats. B-GYKI-38
fiber.
It
side-effects in conscious
233 proved to be a very active
antiarrhythmic
compound which possessed both Class I c and Class III properties according to our investigations.
REFERENCES
KUrthy M., G. Rabloczky, A. Varr6, L. Szathm~ry, L. Jaszlits J. Wellmann, I. ~rczi; Advances Pharmacol. Res. and Practice. Proc. 4th Congr. of Hung. Pharmacol. Soc. Vol. I: Sec. 2. Pharmacol of the vascular system, 211-215, 1985. Varr6 A., G. Rabloczky, M. KHrthy, L. Jaszlits, I. ~rczi; Abstracts of Xth Congr. IUPHAR, Sydney, Australia, PI4D76, 1987.