Berbanes: a new class of selective alpha 2-adrenoceptor antagonists

The alpha-adrenoceptor blocking properties of some berbanes have been studied and compared with those of idazoxan, yohimbine, phentolamine, and prazosin. Their effects on presynaptic alpha 2-adrenoceptors were studied on chemical neurotransmission of isolated rat vas deferens and longitudinal muscle strip of guinea pig ileum; xylazine or norepinephrine was employed as agonist. The alpha 1-adrenoceptor blocking activities of the berbanes were tested on isolated rat vas deferens and rabbit pulmonary artery by using phenylephrine or norepinephrine as agonist. The antagonistic activity of the berbanes and the reference compounds on alpha 2- and alpha 1-adrenoceptors was characterized by the apparent pA2 values. Of the compounds studied, [8aS*-(8a alpha,12a alpha,13a alpha)]-11 alpha-hydroxy-5,6,8a,9,10,11,12a,13,13,a-decahydro-8H-benzo[g]-1,3 -benzodioxolo[5,6-a]quinoli zine, 6d, proved to be the most selective antagonist at the presynaptic alpha 2-adrenoceptors (alpha 1:alpha 2 ratio = 1659). Since blockade of alpha 2-adrenoceptors located on noradrenergic axon terminals leads to an increase of norepinephrine release, this compound could have potential as an antidepressant agent.