Effect of higenamine on alpha-adrenoceptors

The apparent dissociation constant (Ki) calculated from competition curves of higenamine (dl-demethylcoclaurine, DMC), isoproterenol (ISO) and phenylephrine with [3H]WB 4101 for alpha1 receptor were found to be 0.3, 13, and 1.7 microM, and that the Ki’s of DMC, ISO and clonidine with [3H]clonidine for alpha2 receptors were 1.6, 7 microM and 5 nM, respectively. These data showed that both DMC and ISO had affinity for alpha receptors. The contractions of anococcygeus nuscles induced by noradrenaline (NA) were reduced by DMC at 5, 10, and 50 microM. The pA2 value was 4.95. In contrast with DMC, ISO also induced dose-dependent contraction of this muscle (EC50=20 microM), but its maximal action was lower than that induced by NA. It seemed that ISO was a partial alpha1 agonist. The electrically induced contractions of the vas deferens were inhibited by DMC, ISO, and clonidine. Their EC50’s were 150 microM, 1.2 microM, and 1.8 nM, respectively. These results indicated that DMC was an alpha1 antagonist and a weak alpha2 agonist while ISO was an agonist of alpha1 and alpha2 adrenoceptors. However, the effect of ISO on alpha2 adrenoceptor was more potent than that on alpha1 receptor.