Tandospirone and alprazolam: comparison of behavioral effects and abuse liability in humans

Tandospirone is a novel nonbenzodiazepine anxiolytic/antidepressant that acts primarily at the serotonin-1A receptor. In the present study, the behavioral effects and abuse liability of tandospirone were characterized relative to those of the benzodiazepine, alprazolam. In an outpatient setting, the acute effects of placebo, tandospirone citrate (40, 80 and 160 mg) and alprazolam (0.5, 1.0 and 2.0 mg) were assessed with a double-blind, cross-over design in 14 male volunteers with histories of sedative drug abuse. Drug effects were assessed on behavioral performance tasks; observer ratings of drug effect; and subject ratings of strength of drug effect, mood and drug liking. Both alprazolam and tandospirone produced comparable dose-related increases in subject- and observer-rated strength of drug effect. The peak drug effect occurred approximately 2 hr after drug administration; the time to peak did not differ between the two drugs. Alprazolam produced greater impairments on psychomotor performance than did tandospirone. Alprazolam produced dose-related increases in subject-rated drug liking; tandospirone, in contrast, produced dose-related increases in subject-rated drug disliking. The highest dose of alprazolam was predominantly classified by subjects as being a benzodiazepine or a barbiturate (71%) in contrast to the highest dose of tandospirone (29%). Across subjects, tandospirone plasma concentrations after a single dose of 160 mg were significantly correlated with several subjective and behavioral measures. The present study demonstrates that tandospirone and alprazolam can be clearly differentiated on the basis of subjective effects and performance measures. The overall profile indicates that tandospirone has a significantly lower abuse liability than does alprazolam.