Stereoselective morphine-like discriminative properties of a new alkylaminonaphthalenic derivative

The morphine-like properties of a series of aminoalkyl- and cycloalkylamino-naphtalenic derivatives of 17-methyl-17-azaequilenine were studied in rats trained to discriminate morphine (5.6 mg/kg IP) from vehicle in a two-lever operant behavioral procedure reinforced by water access. It was found that one of the compounds tested (i.e., A8; 1-ethyl-1-hydroxy-1-[2-(6-hydroxynaphthyl)]-2-methyl-3- dimethylaminopropane) fully generalized for the morphine stimulus. The discriminative effects of A8 were stereospecific, as indicated by the fact that (+)-(1R,2R)-A8 was three times more potent than the racemic compound and that the (-)-(1S,2S) enantiomer was completely inactive. (+)-(1R,2R)-A8 generalization for the morphine cue was inhibited by naloxone. None of the other five derivatives examined generalized for the morphine stimulus. In conclusion, the naphthalenic structure is a source of compounds with stereospecific and naloxone-reversible morphine-like properties.