Abecarnil and alprazolam in humans: behavioral, subjective and reinforcing effects.
Abecarnil, a novel beta-carboline, is under development for the treatment of Generalized Anxiety Disorder. This study compared the behavioral, subjective and reinforcing effects of abecarnil to those of the benzodiazepine alprazolam in 14 healthy males with histories of sedative drug abuse. Placebo, abecarnil (10, 20, 40 mg) and alprazolam (1.0, 2.0, 4.0 mg) were administered p.o. in a double-blind, cross-over design. Abecarnil and alprazolam produced comparable dose-dependent decreases in behavioral performance on balance, circular lights, digit-recall and digit-symbol-substitution tasks that peaked 2-4 hr after drug administration. Both drugs produced a profile of sedative effects and were categorized by subjects as predominantly barbiturate- or benzodiazepine-like. However, the high dose of alprazolam increased subject-ratings of sleepy, fatigued and tired; these ratings were significantly different from both placebo and all doses of abecarnil. Abecarnil and alprazolam produced comparable dose-dependent increases in ratings of drug strength. The highest dose of alprazolam produced increases in Next Day ratings of drug liking, good effects, monetary value of the drug, and desire to take the drug again that were significantly greater than placebo and the highest dose of abecarnil. Abecarnil, but not alprazolam, produced increases in Next Day ratings of "bad effects" that were significantly greater than placebo. The highest dose of alprazolam produced increases in a direct measure of drug reinforcement (drug vs. money Multiple-Choice Procedure) that were significantly greater than placebo and all doses of abecarnil. Collectively, these data suggest that abecarnil may have less potential for abuse than alprazolam in a sedative-abusing population.
Mumford
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Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Rush
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CR
Griffiths
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D000328:Adult; D000525:Alprazolam / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001519:Behavior / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D012054:Reinforcement, Psychology; D019966:Substance-Related Disorders
D014151:Anti-Anxiety Agents; D002243:Carbolines; C062769:abecarnil; D000525:Alprazolam