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Caffeine is a widely-consumed psychoactive substance whose stimulant effects on mood, attention and performance are largely recognised. The central nervous system pharmacodynamic profile of a single oral dose of a new slow release (SR) caffeine formulation (600 mg) was assessed in a randomised, double-blind, crossover, placebo-controlled study. Twelve young, health, male, sleep-deprived (for 36 h) subjects were studied using EEG and various measures of psychomotor and cognitive functions, including critical flicker fusion (CFF), choice reaction task (CRT), tracking, continuous performance task (CPT), Stroop test, body sway and subjective evaluation (Stanford Sleepiness Scale). Caffeine significantly ( < 0/05) antagonised the detrimental effects of sleep-deprivation on EEG (i.e. produced a significant decrease in delta and theta relative power and a significant increase in alpha and beta (12-40 Hz) relative power) and psychomotor performance (significant increase in speed of reaction on the CRT and Stroop tests, significant decrease in body sway, significant increase in accuracy of the CPT and significant reduction in subjective sedation) compared to placebo. The effect peaked 4 h after dosing and was maintained until the end of sleep deprivation (i.e. 24 h after dosing). In conclusion, the present results demonstrate that a single dose of caffeine SR possesses alerting effects which are able to reverse the deleterious effect of 36 h sleep deprivation for at least 24 h. Copyright 2000 John Wiley & Sons, Ltd.

Venlafaxine is currently marketed for treatment of depressive disorders as a conventional tablet formulation with a twice or three times daily dosage regimen. The absolute bioavailability of the conventional (CF) and extended-release (XR) formulations and their effects on electroencephalograms (EEG) and on a visual analog scale (VAS) for nausea were assessed in a randomized, double-blind, four-way crossover, placebo-controlled study of 16 healthy young men who were given either a single oral dose of 50 mg of CF venlafaxine, 75 mg of XR venlafaxine, or an intravenous dose of 10 mg of venlafaxine, or a placebo at 1-week intervals. The absolute bioavailability of venlafaxine was between 40% and 45% and was similar for both the CF and XR formulations. Venlafaxine produced central effects of a desipramine-like antidepressant. Regardless of formulation tested, the main EEG changes were an increase in fast beta (20-30 Hz) energy, which was more pronounced over the frontotemporal regions and extended within the full beta range (16-40 Hz). Maximum effect was reached at 6 hours for the CF and reached a plateau from 10 to 24 hours for the XR formulation. A dose-proportional increase in central activity, expressed as area under the effect curve (AUE) of the beta band, was observed between the CF (50 mg) and XR (75 mg) formulations. Compared with the CF tablet, the XR formulation also produced a much less intense maximum effect and a decrease of 63% in the AUE of nausea normalized by dose. The XR formulation has the same absolute bioavailability and the same central activity as assessed by EEG, but produced less intensive nausea than CF venlafaxine. The present findings suggest that a once-daily dosage regimen should be sufficient. This was confirmed by several clinical trials in depressive patients.

Purpose: To study the effects of iobitridol, a nonionic contrast medium, on the electrocorticography and the blood-brain barrier structure in rabbits., Methods: Iobitridol was compared with isoosmolar mannitol and isotonic saline after selective injection (2.5 mL per rabbit in 30 seconds) into the internal carotid artery in the rabbit (six per group). The electrocorticograms (two frontooccipital leads) were then subjected to spectral analysis (fast Fourier transform). Evans blue dye served as a marker of blood-brain barrier damage., Results: No blood-brain barrier damage was found, regardless of the treatment administered. Selective catheterization induced an increase in slow waves (0 to 4 Hz). Analyzed both spectrally (distribution of frequency bands, position of the maximum peak with respect to the distribution, and cerebral electric power) and conventionally, iobitridol did not modify the electrocorticograph parameters in the animals. This also applied to the mannitol and saline solutions., Conclusion: No chemotoxic effects of iobitridol were found.

The use of hypnotics to optimize rest periods during sustained operations could be of help to military personnel. Zolpidem, an imidazopyridine hypnotic, was evaluated for its residual effects on daytime wakefulness in 12 subjects belonging to ground air force personnel and 12 navy fighter pilots. In this controlled double blind crossover study, each subject randomly received zolpidem 10 mg, flunitrazepam 1 mg or placebo, in three separate sessions, 1 week apart at 10 p.m. or 1 a.m., respectively. The absence of residual effects after zolpidem intake was attested by subjective assessments, psychomotor tests (including a simulated flight), and EEG analysis showed that this hypnotic could be considered for operational use.

(+/-)-1-(Isopropylamino)-3-[p-(2-cyclopropyl-methoxyethyl)-phenoxy]-2-propanol HCl (betaxolol, SL 75212) was given to groups of healthy volunteers, 10 mg daily for 7 days followed by 20 mg daily 7 days in one group, and increasing daily doses up to 60 mg/day for a total of 15 days in the other group. The pharmacokinetics were studied during dosing and in the washout period. The pharmacokinetic characteristics were unchanged after repeated doses, T/2 16-22 h, Vd 7.7-8.8 l/kg; clearance 0.28-0.33 l/h/kg.