Basic and applied studies on cardiotonic

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During recent years there have been numerous effeors to find and develop novel cardiotonic agensts that are more effeorive and more selective than the cardiac glycosides or catecholamines. [8]-Gingerol produced a concentration-dependent positive inotropic effect on guinea pig isolated left atria. The inotropic effect of gingerol was abolished by ryanodine. Furthermore, our pharmacological studies suggest that the enhancement of the Ca^<2+>-pumping activity of sarcoplasmic reticulum (SR) plays an important role in the cardiotonic action of gingerol. We synthesized gingerol related compounds (AP-004, AP-005 and AP-015) and investigated the effects of these compounds on the Ca^<2+>-ATPase activity of SR.The Ca^<2+>-ATPase activity and the Ca^<2+>-pumping activity increased by these compounds in a concentration-dependent manner. It is probable that both o-methoxy phenol and hydeocarbon chain in the molecule of gingerol analogues are a request for activation of the Ca^<2+>-pumping ATPase.In … More the course of our survey of cardiotonic substances from natural sources having unique mechanism of action, xestoquinone (XQN) was isolated and purified as a powerfully cardiotonic principle of an Okinawa sea sponge Xestospongia sapra. Our pharmacological data suggest that an enhancement of intracellular cyclic AMP content and Ca^<2+> influx across the cell membrane contribute to the late phase of XQN-caused cardiotonic responses, wheres the early phase may largely be elicited through direct activation of contractile elements. XQN may provide an novel leading compound for valuable cardiotonic agents. Unlike N-ethylmaleimide, modification of 2 mol of SH groups per myosin by xestoxinone caused a marked increase in the actomyosin ATPase activity. XQN modifies the specific SH groups in myosin distinct from SH_1 and SH_2, resulting in activation of actocyosin ATPase.The crude acetone extract of the fruits of Evodia retaecarpa Bentham (Rutaceae) exhibited a positive inotropic effect with a novel mechanism on the guinea pig isolated left atria. Less