Synthesis and biological activity of thienodiltiazem in isolated heart muscle preparations of guinea pigs.
The new compound thienodiltiazem was synthesized and investigated regarding structure-activity relations and calcium antagonistic properties. Isometric contraction force was measured in guinea-pig papillary muscles and chronotropic activity was studied in right atria of guinea pigs. Compared to the parent drug diltiazem (CAS 42399-41-7) the thieno derivative had a more potent negative chronotropic effect on spontaneously beating right atria and a more potent inotropic effect on papillary muscles. The negative inotropic action was reversed by increasing the extracellular calcium concentration.
Handler
Norbert
N
Department of Pharmaceutical and Medicinal Chemistry, University of Vienna, Vienna, Austria.
Erker
Thomas
T
Lemmens-Gruber
Rosa
R
Studenik
Christian R
CR
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002122:Calcium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007537:Isometric Contraction / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D013841:Thiazepines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*
C528625:4-(2-dimethylaminoethyl)-4,5,6,7-tetrahydro-7-(4-methoxyphenyl)-5-oxothieno(2,3-b)(1,4)thiazepin-6-yl acetate; D002121:Calcium Channel Blockers; D007202:Indicators and Reagents; D013841:Thiazepines; D013876:Thiophenes; D002122:Calcium Chloride