[Studies on cardiac ingredients of plants. VIII. Preparation of nitrates of proscillaridin and their pharmacological activities].
To reduce the vascular contracting effect of the cardiac glycoside, proscillaridin (1), all kinds of its nitrates were prepared by utilizing effectively an isopropylidene function as a protective group. The pharmacological activities of proscillaridin nitrates were evaluated by the use of isolated guinea-pig papillary muscle preparations and Na+,K(+)-adenosine triphosphatase preparations from the dog kidney. Furthermore, the effect for smooth muscle using the helical strips isolated from 13-week old spontaneously hypertensive rat was examined. The positive inotropic effects and Na+, K(+)-adenosine triphosphatase inhibition activities of mononitrates (6, 9, 15) and dinitrates (3, 4, 5) were a little less potent than 1, but those of trinitrate (2) were much reduced. Every nitrate did not exhibited a vascular contracting effect but a relaxing effect. Among them, the vascular relaxing effects of 2',3'-dinitrate (3) and 2',4'-dinitrate (4) were more potent than those of the other nitrates.
Murakami
N
N
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Sato
Y
Y
Tanase
T
T
Nagai
S
S
Ueda
T
T
Sakakibara
J
J
Ando
H
H
Hotta
Y
Y
Takeya
K
K
Asano
M
M
D000818:Animals; D004071:Digitalis Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009566:Nitrates / Q000138:chemical synthesis* / Q000494:pharmacology; D011442:Proscillaridin / Q000138:chemical synthesis* / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D004071:Digitalis Glycosides; D009566:Nitrates; D000254:Sodium-Potassium-Exchanging ATPase; D011442:Proscillaridin