The discriminative stimulus properties of the R2 isomer of viminol

Viminol is a pyrrylethanolamine derivative which exists naturally as a racemic mixture containing six different stereoisomers. Viminol has been reported to exert both potent analgesic activity and minimal dependence liability. The analgesic component of racemic viminol has been attributed to the R2 isomer, while the antagonistic S2 isomer appears to be responsible for minimizing the dependence liability of the racemate. We tested the R2 isomer of viminol in rats trained to discriminate 3 mg/kg morphine sulfate from saline on a VI-15 sec schedule for sweetened milk reinforcement. The R2 isomer resulted in dose dependent morphine-like responding, with complete generalization to the 2.5 mg/kg dose of R2 viminol. The morphine-like discriminative stimulus properties of R2 viminol were reversed by naloxone in a dose-dependent fashion, with total blockade by 0.1 mg/kg naloxone. R2 viminol, like morphine, also had a biphasic effect on response rate with low doses increasing and high doses suppressing response rates. R2 viminol had a overall shorter time course than that reported for morphine, and its different physiological and behavioral effects may not occur simultaneously. These data suggest that R2 viminol exerts a subjective effect similar to that of morphine and supports the hypothesis that R2 viminol has opiate activity despite its lack of structural relationship to the opiate series.