A number of selective α₂-adrenoceptor antagonists have been prepared on the basis of the lead structure rauwolscine (I), which, along with its isomer yohimbine, was one of the first compounds found to display a reasonable degree of selectivity for antagonism of the α₂-adrenoceptor vs the α₁-adrenoceptor. These include the benzoquinolizine WY 26703 (2) and several recently reported octahydro-2H-benzo[b]furo[2,3-a]quinolizine and berbane derivatives. In addition, idazoxan (2-(1,4-benzodioxan-2-yl)-2-imidazoline) and related compounds, which are structurally unrelated to rauwolscine, have been shown to be selective α₂-adrenoceptor antagonists. Such agents are of current interest for their role in elucidating the pharmacological and physiological significance of α₂-adrenoceptors and for their potential clinical utility for the treatment of a number of diseases including depression. We now wish to describe the synthesis and preliminary pharmacological evaluation of (8aa,12aa,13aa)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy-12-(methylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine (8a), a structural hybrid between rauwolscine and WY 26703. This tetracyclic compound, which has been resolved to afford the active enantiomer 8b, is a remarkably selective and potent α₂-adrenoceptor antagonist.