Indiplon [N-methyl-N-[3-[3-(2-thienylcarbonyl)-pyrazolo[1,5-alpha]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 alpha(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.