N-substituted octahydro-4a-(3-hydroxyphenyl)-10a-methylbenzo[g]isoquinolines are opioid receptor pure antagonists

N-Methyl- and N-phenylethyl-(+/-)-1,2,3,4,4a,5,10,10a-octahydro-4a-(3-hydro xyphenyl)-10a-methyl- benzo[g]isoquinolines (4 and 5, respectively) were fo und to be pure opioid antagonists. These compounds were shown to share many of the characteristics identified with the N-methyl- and N-phenylethyl tra ns-3,4-dimethyl-4(3-hydroxyphenyl)piperidine (1 and 2, respectively) includ ing N-substituent mediated potency and a lack of N-substituent mediated ant agonism. These data suggest that compounds 4 and 5 and the N-substituted tr ans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (1 and 2) may interact with opioid receptors similarly. (C) 1998 Elsevier Science Ltd. All rights rese rved.