Relative abuse liability of indiplon and triazolam in humans: A comparison of psychomotor, subjective, and cognitive effects

Lawrence P. Carter, Roland R. Griffiths, Patricia E. Suess, John H. Casada, Christopher L. Wallace, John D Roache

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Indiplon [N-methyl-N-[3-[3-(2-thienylcarbonyl)-pyrazolo[1,5-α] 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 GABAA receptors containing an α1 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 participant-rated 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.

Original languageEnglish (US)
Pages (from-to)749-759
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume322
Issue number2
DOIs
StatePublished - Aug 2007

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Triazolam
GABA-A Receptors
Pharmaceutical Preparations
indiplon
Psychomotor Disorders
Residential Facilities
Psychomotor Performance
Sleep Initiation and Maintenance Disorders
Benzodiazepines
Substance-Related Disorders
Volunteers

ASJC Scopus subject areas

  • Pharmacology

Cite this

Relative abuse liability of indiplon and triazolam in humans : A comparison of psychomotor, subjective, and cognitive effects. / Carter, Lawrence P.; Griffiths, Roland R.; Suess, Patricia E.; Casada, John H.; Wallace, Christopher L.; Roache, John D.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 322, No. 2, 08.2007, p. 749-759.

Research output: Contribution to journalArticle

Carter, Lawrence P. ; Griffiths, Roland R. ; Suess, Patricia E. ; Casada, John H. ; Wallace, Christopher L. ; Roache, John D. / Relative abuse liability of indiplon and triazolam in humans : A comparison of psychomotor, subjective, and cognitive effects. In: Journal of Pharmacology and Experimental Therapeutics. 2007 ; Vol. 322, No. 2. pp. 749-759.
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abstract = "Indiplon [N-methyl-N-[3-[3-(2-thienylcarbonyl)-pyrazolo[1,5-α] 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 GABAA receptors containing an α1 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 participant-rated 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.",
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