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BEHAVIORAL PHARMACOLOGY

Relative Abuse Liability of Indiplon and Triazolam in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects

Departments of Psychiatry and Behavioral Sciences (L.P.C., R.R.G., P.E.S.) and Neuroscience (R.R.G.), Johns Hopkins University School of Medicine, Baltimore, Maryland; and Departments of Psychiatry (J.H.C., C.L.W., J.D.R.) and Pharmacology (J.D.R.), University of Texas Health Science Center at San Antonio, San Antonio, Texas

Indiplon [N-methyl-N-[3-[3-(2-thienylcarbonyl)-pyrazolo[1,5-]pyrimidin-7-yl]phenyl]acetamide; NBI 34060] is a positive allosteric GABA_A receptor modulator that is under development for the treatment of insomnia. This study compared the abuse potential of indiplon, a compound with preferential affinity for GABA_A receptors containing an ₁ subunit, with triazolam in 21 volunteers with histories of drug abuse. Placebo, triazolam (0.25, 0.5, and 0.75 mg), and indiplon (30, 50, and 80 mg) were studied in counterbalanced order under double-blind conditions at two different residential research facilities. Both drugs impaired psychomotor and cognitive performance and produced similar dose-related increases in participant and observer ratings of drug strength. The onset of action of both drugs was rapid (30 min); however, the duration of action of indiplon (3–4 h) was shorter than that of triazolam (4–6 h). The profiles of subjective effects of triazolam and indiplon were similar; however, a maximum of 52% of participants identified indiplon as a benzodiazepine or barbiturate, compared with 81% of participants after 0.75 mg of triazolam. On participantrated subjective effects relevant to sedation, the slope of the triazolam dose-effect curve was significantly steeper than that of indiplon. Neither the largest doses of indiplon and triazolam nor the slope of the indiplon and triazolam dose-effect curves were significantly different from each other on any of the same-day or next-day measures of positive drug effects or next-day measures of reinforcing effects. Together, these data suggest that although the abuse potential of indiplon is not different from that of triazolam at these doses, psychomotor and cognitive impairment after large doses of indiplon might be less.

Address correspondence to: Dr. John D. Roache, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., MC7793, San Antonio, TX 78229. E-mail: roache{at}uthscsa.edu

This article has been cited by other articles:

				J. C Marrs Indiplon: A Nonbenzodiazepine Sedative-Hypnotic for the Treatment of Insomnia Ann. Pharmacother., July 1, 2008; 42(7): 1070 - 1079. [Abstract] [Full Text] [PDF]