Thirty healthy volunteers participated in this two-part study. Part 1 was a single-blind, two-period crossover design to determine the effects of a single dose of ethanol (0.03% < BAC < 0.05%) or ethanol-placebo on driving ability, memory, and psychomotor performance. Part 2 was a double-blind, five-period crossover design to measure the effects of a middle-of-the-night administration of zaleplon 10 or 20 mg, zolpidem 10 or 20 mg, or placebo on driving ability 4 hours after administration and memory and psychomotor performance 6 hours after administration. The on-the-road driving test consisted of operating an instrumented automobile over a 100-km highway circuit at a constant speed (95 km/h) while maintaining a steady lateral position between the right lane boundaries. The standard deviation of lateral position (SDLP) was the primary performance parameter of the driving test. The psychomotor and memory test battery consisted of the Word Learning Test, the Critical Tracking Test, the Divided Attention Test, and the Digit Symbol Substitution Test. Data for each part were analyzed separately using ANOVA for crossover designs. Zaleplon 10 and 20 mg did not significantly impair driving ability 4 hours after middle-of-the-night administration. Relative to placebo, after zolpidem 10 mg, SDLP was significantly elevated, but the magnitude of the difference was small and not likely to be of clinical importance. Memory and psychomotor test performance was unaffected after both doses of zaleplon and zolpidem 10 mg. In contrast, zolpidem 20 mg significantly increased SDLP and speed variability. Further, zolpidem 20 mg significantly impaired performance on all psychomotor and memory tests. Finally, driving performance, Digit Symbol Substitution Test, Divided Attention Test, and immediate and delayed free recall of the Word Learning Test were significantly impaired after ethanol. The results show that zaleplon (10 and 20 mg) is a safe hypnotic devoid of next-morning residual impairment when used in the middle of the night.

Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom completed the study, received venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three times a day) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose increments, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for confirming compliance. Venlafaxine had no significant effect on the primary driving parameter (standard deviation of lateral position) and failed to impair psychomotor performance. Mianserin profoundly and consistently impaired driving and psychomotor performance. However, both drugs significantly impaired vigilance performance. Maximal effects occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both series. The increment in venlafaxine's dose on day 8 did not increase this effect. The drug's selectively impairing effect on vigilance is shared by other "serotonergic" anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly monotonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use by patients who drive.

Multiple AMLs show more growth than solitary AMLs.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Body sway increases in older adults and may lead to an increase in the risk of falling.• The problem of impaired stability in the elderly may be compounded by the use of hypnotics, which have been associated with an increased risk of next-day falls as well as drowsiness.• The potential adverse effects of hypnotic drugs on steadiness may be exacerbated during the night, in the event that an individual needs to get out of bed. WHAT THIS STUDY ADDS• This study examines the effects of gaboxadol (an investigational treatment for insomnia), zolpidem (a current hypnotic included as an active control) and placebo on body sway and attention/information processing ability following bedtime dosing in elderly subjects who were woken during the night for assessments.• Zolpidem and gaboxadol increased body sway at various time points during the night relative to placebo; at 1.5 h post dose, the time of peak concentrations of both drugs, gaboxadol produced less impairment than zolpidem.• Compared with placebo, neither gaboxadol nor zolpidem impaired attention/informationprocessing ability as assessed by critical flicker fusion. AIMSTo evaluate tolerability, pharmacokinetics and night-time effects on body sway and critical flicker fusion (CFF) of gaboxadol following bedtime dosing in healthy elderly subjects. METHODSSubjects (17 women, seven men) aged 65-75 years received gaboxadol 10 mg, zolpidem 5 mg (active control) or placebo at 22.00 h in a three-period, randomized, double-blind crossover study. They were awakened during the night for evaluation of body sway and CFF. Pharmacokinetics of gaboxadol were assessed during a fourth single-blind treatment period. Adverse events were recorded throughout the study.

Administration of sumatriptan intranasally at doses of 10 mg and 20 mg by the breath actuated bi-directional powder delivery device results in rapid absorption. Delivery to target sites beyond the nasal valve induced a similar EEG profile to subcutaneous sumatriptan 6 mg and prevented migraine attacks in patients following GTN challenge. Intranasal administration of sumatriptan powder with the breath actuated bi-directional powder delivery device was well tolerated.

Administration of sumatriptan intranasally at doses of 10 mg and 20 mg by the breath actuated bi-directional powder delivery device results in rapid absorption. Delivery to target sites beyond the nasal valve induced a similar EEG profile to subcutaneous sumatriptan 6 mg and prevented migraine attacks in patients following GTN challenge. Intranasal administration of sumatriptan powder with the breath actuated bi-directional powder delivery device was well tolerated.

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