| Summary: | 博士 === 國立臺灣大學 === 藥理學研究所 === 84 === In previous screeing study,many isoquinoline and pavine
alkakiuds were isolated.To assess the antiarrhythmic potential
electro- physiological actions of these agents on cardiac
tissues were ex- aminted.S49,CSH087 and CSH068 are
benzylisoquinoline derivatives. S49,CSH087 and CSH068 prolong
the action potentiabl durations(APD )Voltage clamp studies
studies revealed the inhibition of the tr- ansient outward
current (Ito)by S49,CSH087 and CSH068,but a lack of effect on
calcium current(Ica).In contrast to Ito,the steady state
outward current (Iss)was more resistant to CSH087 and S49, but
blocked by CSH068 INa was also inhibited ty these agen.S49 in
-hibited Ito,enhanced Ito decay,but without effect on half
inac- tio voltage(V0.5)and slope factor(S) of the inaction
curve.S49 developed a block during the depolarization step in
amonoexponen tial during the depolarization step in a
monoexponential manner. The results suggest that S49 exerts
open state block of Ito.The relief from quinidine or S49-
induced block was assessed and compared.The relief from the
block of Ito by S49 was faster (-)-Caryachine(CNMe)is a pavine
alkaloid,isolated from Crypto- carya chinensis Hemsl.It
suppressed the action potential upstroke(Vmax)and prolonged the
action potential duration(ADP) thrangh the inhibition of INa.
and Ito.CNMe reduced the INa with a negative-shift of its
inactivation curves and slowing of its recovery from
inactivation. CNMe effectively inhibited ischemia reperfusion
induced ventricular tachycardia.The inhibition of INa and Ito
may contribute to this antiarrhythmic activity.We further
compared the inhibition of INa by 3um CNMe,10um lidocaine and
3um quinidine.At these concentrations they caused similar tonic
block of INa.At prepulse duration of 400ms CNMe exerted higher
used-dependent block of INa than quinidine. The onset rat of
INa block by CNMe is slower. Nevertheless,the rate of
relieving block by CNMe is faster.
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