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Selective Inhibition of Calcium Entry Induced by Benzylisoquinolines in Rat Smooth Muscle

Abstract— The mechanism of relaxant activity of six benzylisoquinolines was examined in order to determine the minimal structural requirements that enable these compounds to have either a non‐specific action like papaverine or an inhibitory activity on calcium entry via potential‐operated channels. All the alkaloids tested totally or partially relaxed KCl‐depolarized rat uterus and inhibited oxytocin‐induced rhythmic contractions. Only glaucine and laudanosine inhibited K+‐induced uterine contractions more than oxytocin‐induced uterine contractions. In Ca+‐free medium, sustained contractions induced by oxytocin or vanadate were relaxed by the alkaloids tested except for glaucine and laudanosine indicating no inhibitory effect on intracellular calcium release. Those alkaloids containing an unsaturated heterocyclic ring (papaverine, papaverinol, papaveraldine, N‐methylpapaverine and dehydropapaverine) exhibited a more specific activity than those with a tetrahydroisoquinoline ring.