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  • 1
    Electronic Resource
    Electronic Resource
    The positive inotropic, antiarrhythmic and Na+, K+-ATPase inhibitory effects of the isoquinoline derivative, BIIA (1980)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 312 (1980), S. 187-192 
    Details
    ISSN: 1432-1912
    Keywords: Isoquinoline derivative BIIA ; Na+, K+-ATPase ; Action potential ; Antiarrhythmic activity ; Positive inotropic action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of the isoquinoline derivative 3-benzylamino-5,6-dihydro-8,9-dimethoxy-imidazo-5,1-a-isoquinoline-hydrochloride (BIIA) were studied in the cat in situ and guinea-pig isolated heart preparations: 1. Administration of BIIA (2 mg/kg i.v.) to anaesthetized cats results in a rapid rise in cardiac (dP/dt)max, decrease in heart rate and increase in systolic and diastolic blood pressure. These effects reach their maximum within a minute and disappear within 20 min. With increasing dosage a depression in the S T-segment of the ECG is observed, being similar to that induced by cardiac glycosides. Toxic doses lead to ventricular flutter and fibrillation. 2. In the concentration range of 0.3–10 μmol/l, BIIA exerts a strong positive inotropic effect in isolated guinea-pig heart preparations which is not mediated via α- or β-adrenoceptors and a negative chronotropic effect in spontaneously beating right atria. 3. BIIA inhibits Na+, K+-ATPase preparations isolated from guinea-pig heart and kidney in the range of 5–100 μmol/l. Unlike that of cardiac glycosides, this inhibition is competitive with Na+. The concentration response curves for the positive inotropic and Na+, K+-ATPase inhibitory effects of BIIA are both one order of magnitude higher in concentration than the respective concentration response curves found for ouabain. 4. BIIA is more potent than quinidine in increasing the threshold for arrhythmia induced by alternating current in isolated guinea-pig atria and papillary muscles. However, at a concentration of 3 μmol/l, BIIA can itself be arrhythmogenic. 5. A delay of repolarisation of the cardiac action potential may account for the antiarrhythmic properties of this drug, whereas strong inhibition of Na+, K+-ATPase and a decrease in resting potential may account for its toxicity at high concentrations. As there is a decrease in the plateau phase of the action potential at positive inotropic concentrations of BIIA, the increase in the force of contraction cannot be explained by alterations in the transmembrane potential, but similar to cardiac glycosides may be attributed to an inhibition of the Na+, K+-ATPase of the cell membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569729
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of (+)- and (±)-sotalol on repolarizing outward currents and pacemaker current in sheep cardiac Purkinje fibres (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 696-704 
    Details
    ISSN: 1432-1912
    Keywords: Sheep Purkinje fibre ; Outward currents ; Pacemaker current ; (+)-Sotalol ; (±)-Sotalol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was aimed to differentiate the action of (+)- and (±)-sotalol (10–1000 μmol/l) on membrane currents which are active during the repolarization of cardiac action potentials Effects where studied in shortened sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique Action potentials were activated at a frequency of 0.25 Hz and membrane currents at 0.03 Hz or 0.05 Hz in most experiments. Out of the currents investigated the transient outward current (ito) reacted most sensitively to (+)- and (±)-sotalol. Ito-amplitude was decreased on the average to 77% of reference at 10 μmol/l and to 53% at 1000 μmol/l (+)- or (±)-sotalol. The maximally available ito-current was decreased but the voltage-dependent control of inactivation was left nearly unchanged. The initial inwardly rectifying current (iKi), which propels the last repolarization phase of the action potential and controls resting potential to a large extent was reduced on the average to 93% of reference at 10 μmol/l and to 62% at 1000 μmol/l (+)- or (±)-sotalol. Time-dependent (delayed) outward current (iK) was on the average not affected by (+)- or (±)-sotalol up to 100 μmol/l and was decreased to 84% of reference current under the influence of 1000 μmol/l. An initial outward current, which is activated at positive membrane potentials (iinst) was not clearly affected by (+)- or (±)-sotalol at concentrations up to 1000 μmol/l Pacemaker current (if) was not influenced by the drugs up to 100 μmol/l. Only at 1000 μmol/l was the amount of available if-current decreased to 79% of reference. (The potential-dependent control of activation was not affected) Time constants of time-dependent currents ito, iK and if did not change in concentrations up to 1000 μmol/l of the drug. Action potential duration increased at (+)- or (±)-sotalol concentrations ≥ 10 μmol/l and maximal prolongation was achieved at concentrations of 100–300 μmol/l Resting potential remained nearly unchanged at these concentrations, but the membranes depolarized at 1000 μmol/l. According to our data action potential prolongation in sheep Purkinje fibres under the influence of (+)- and (±)-sotalol correlates to the drug-induced block to ito-current and inwardly rectifying iK1-current.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00717747
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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