Tetrandrine and isotetrandrine, two bisbenzyltetrahydroisoquinoline alkaloids from Menispermaceae, with rat uterine smooth muscle relaxant activity.
The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S,1'S tetrandrine and its isomer 1R,1'S isotetrandrine, were investigated in rat isolated uterus in order to identify the mechanism of relaxant action and to study the influence of the absolute configuration on the activity of these alkaloids. Both inhibited the uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca(2+)-free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin but tetrandrine did not. The relaxant effects of the alkaloids may be due to blockade of calcium influx through specific channels. Tetrandrine and isotetrandrine modify the calcium channel in a nonreversible manner whilst only isotetrandrine acts intracellularly. Tetrandrine shows a more specific relaxant activity as a calcium entry blocker.
Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Spain.
P
P
D'Ocón
M A
MA
Blázquez
A
A
Bermejo
E
E
Anselmi
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D044182:Benzylisoquinolines; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects; D010121:Oxytocin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects*
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; C009438:tetrandrine; D010121:Oxytocin; D000109:Acetylcholine