Highway driving performance and cognitive functioning the morning after bedtime and middle-of-the-night use of gaboxadol, zopiclone and zolpidem.
Gaboxadol is a selective extrasynaptic GABA(A) receptor agonist previously in development for the treatment of insomnia. Due to its short half-life (1.5-2 h) it is expected to be free from residual effects the next morning. The present study assessed the residual effects of evening and middle-of-the-night administration of 15 mg of gaboxadol on cognitive, psychomotor and driving performance. Twenty-eight healthy volunteers entered the study with 25 (12 women; mean age 31.4 years) completing a double-blind, placebo-controlled, active-referenced five-way cross-over study. Each treatment night subjects ingested one capsule at 23:00 hours and one at 04:00 hours. Treatments were placebo at both times, 15 mg gaboxadol or 7.5 mg zopiclone followed by placebo, and placebo followed by 15 mg gaboxadol or 10 mg zolpidem. Effects on cognition and psychomotor performance were assessed between 07:30 and 08:30 hours and on driving between 09:00 and 10:00 hours. Driving, as measured by standard deviation of lateral position in an on-the-road driving test, was almost significantly (P < 0.07) impaired after evening administration of gaboxadol for the all-subjects-completed set (n = 25) but significantly (P < 0.05) in the full analysis set (n = 28). Effects of all other active treatments on driving were significant. Evening administration of gaboxadol had minor effects on divided attention only, whereas middle-of-the-night administration impaired performance significantly in all tests except memory. Zolpidem and zopiclone impaired performance significantly in every test except tracking after zopiclone; 15 mg of gaboxadol can produce minor residual effects on driving after evening administration. Administration later at night is associated with moderately impairing residual effects on driving and psychomotor performance but not on memory.
Leufkens
Tim R M
TR
Experimental Psychopharmacology Unit, Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands. t.leufkens@maastrichtuniversity.nl
Lund
Jesper S
JS
Vermeeren
Annemiek
A
D000328:Adult; D000339:Affect / Q000187:drug effects; D001143:Arousal / Q000187:drug effects*; D001288:Attention / Q000187:drug effects*; D001334:Automobile Driving / Q000523:psychology*; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009483:Neuropsychological Tests; D009949:Orientation / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D011930:Reaction Time / Q000187:drug effects; D012153:Retention, Psychology / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D055815:Young Adult; D000077334:Zolpidem
D053961:Azabicyclo Compounds; D018755:GABA Agonists; D007555:Isoxazoles; D010879:Piperazines; D011725:Pyridines; C515050:zopiclone; D000077334:Zolpidem; C015542:gaboxadol