Blocking actions of l-stephanine, xylopine and 7 other tetrahydroisoquinoline alkaloids on alpha adrenoceptors

The blocking action and selectivity of 9 tetrahydroisoquinoline alkaloids on alpha adrenoceptors have been investigated in isolated tissues. Dehydrostephanine and berbamine suppressed the inhibition of clonidine for the electrically stimulated twitch response of rat vas deferens, with pA2 values of 5.36 and 5.49, respectively. l-Crebanine, l-tetrahydrocoptisine, berberine, l-stepholidine and l-tetrahydropalmatine had obvious blocking effects on alpha 1 and alpha 2 adrenoceptors. l-Stephanine and xylopine could competitively inhibit anococcygeus muscle contraction induced by phenylephrine with pA2 values of 6.76 and 6.68, respectively. These 2 alkaloids showed no effect on the inhibition of clonidine for contractile response of rat vas deferens to field stimulation, and their selectivity ratios to block alpha 1 and alpha 2 adrenoceptors were 57.5 and 47.9, respectively. These results indicate that l-stephanine and xylopine are 2 potent and highly selective alpha 1 adrenoceptor blockers.