Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors

Summary A series of 3,8-diazabicyclo (3.2.1) octanes (DBO) ( 1 ) substituted at the nitrogen atoms by acyl and aralkenyl groups, were tested in in vitro binding assays towards μ and δ opioid receptors. The most representative terms ( 1a , 1d , 1g , 1j ,) were also evaluated for the analgesic potency in vivo by the hot plate method. Among the compounds tested the most potent was the p.nitrocinnamyl DBO ( 1d ) which displayed a μ/δ selectivity and an analgesic activity respectively 25 and 17 fold those of morphine. On the contrary, the m.hydroxycinnamyl DBO ( 1g ) was markedly less active as agonist than the parent 1a , thus suggesting that structure 1 interacts with opioid receptors in a different fashion than morphine. Compound 1j isomer of 1a which is provided with high μ affinity, but lower analgesic potency, was found to possess a mixed agonist-antagonist activity.