STUDIES ON CARDIAC INGREDIENTS OF PLANTS .13. CHEMICAL MODIFICATION OF GITOXIN TO CARDIOTONIC COMPOUNDS WITHOUT VASCULAR CONTRACTILE EFFECT

Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl chain at C-3 of the steroid nucleus (10) were prepared from git oxin (I), The pharmacological activities of the resulting compounds (4 and 10) were evaluated by measurement of inhibitory effect on Na+, K-adenosine triphosphatase (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated guinea-pig papillary muscle prepara tions, and the effect on smooth muscle using the mesenteric artery fro m spontaneously hypertensive rats, Most of the compounds showed a smal ler contractile effect on the arterial muscle, Among these compounds, gitoxin 3 ''-nitrate (4g) exhibited the most desirable biological acti vities, such as PIE comparable to that of 1, 1.25 times wider concentr ation-dependent range than 1, and lack of contractile activity on vasc ular muscle.