Selective chiral inhibition of Ca2+ entry promoted by bisbenzyltetrahydroisoquinolines in rat uterus.
The effects of diltiazem and six bisbenzyltetrahydroisoquinoline alkaloids (antioquine, 7-O-methylantioquine, dimethylantioquine, monterine, granjine and cordobimine) were studied in rat isolated uterus in order to clarify the mechanisms of their relaxant actions. All the compounds tested completely relaxed KCl-induced contractions and totally or partially inhibited oxytocin-induced rhythmic contractions. Only alkaloids with absolute configurations (1R,1'S or 1R,1'R) acted intracellularly, promoting relaxation of contractile responses induced by oxytocin in a Ca(2+)-free medium, as does papaverine. Alkaloids of the antioquine series (1S,1'R) selectively inhibited Ca2+ entry. The great rigidity of these structures and their stereoselective action make these alkaloids useful in studies of the conformational features of the Ca2+ channel.
Ivorra
M D
MD
Department de Farmacologia, Facultat de Farmacia, Universitat de València, Spain.
Cercós
A
A
Zafra-Polo
M C
MC
Perez-Prieto
J
J
Sáez
J
J
Cortes
D
D
D'Ocon
P
P
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D009126:Muscle Relaxation / Q000187:drug effects; D010121:Oxytocin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D010121:Oxytocin; D011189:Potassium Chloride; C059733:antioquine; D004110:Diltiazem