Comparison of the pharmacologic action of two isoquinoline alkaloids on rat cardiac tissue

Abstract

We investigated the action of two synthetic isoquinoline alkaloids, 3,4-dihydroxybenzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CSH109) and 2-bromo-3,4-dimethoxybenzyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (CSH118) on rat cardiac tissue. In the right atria, CSH109 increased the amplitude of contractions and spontaneous beats dose-dependently. In the driven left atria and right ventricular strips, CSH109 caused a similar increase in contractions. The positive inotropic and chronotropic actions of CSH109 were antagonized by propranolol. CSH118 caused the spontaneous beats in the right atria to slow down. CSH118, however, failed to antagonize the positive inotropic effect and positive chronotropic effect of isoprenaline. Electrophysiologic study revealed that 3 microM CSH118 markedly reduced fast action potential upstroke and prolonged the action potential duration (APD50) of rat ventricular cells from 34 +/- 8 msec to 122 +/- 29 msec (n = 6). CSH109 prolonged APD50 slightly from 24 +/- 4 msec to 38 +/- 7 msec (n = 4). Under voltage clamp conditions, CSH109 significantly increased the L-type calcium inward current (ICa). The TTX-sensitive sodium inward current (INa), transient outward (Ito) and late outward current (I800), however, were unaffected. The increase in ICa by CSH109 was effectively antagonized by propranolol. Contrary to the action of CSH109, CSH118 strongly suppressed INa, ICa, Ito and I400. The inhibition of INa by 1.5 to 9 microM CSH118 was associated with negative shifting of its steady state inactivation curve. It is concluded that CSH109 exerts a cardiac effect by activating the B-adrenoceptor. CSH118, however, is a broad spectrum ionic channel blocker.