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The aim of this study was to investigate the cognitive and electroencephalography (EEG) short-term effects of a calcium antagonist, nicardipine, compared to placebo and clonidine (which, having known sedative effects, acted as a negative control) for 15 days in elderly hypertensive patients with memory complaints. Nicardipine and clonidine were compared with placebo in a double-blind, randomized, three-way cross-over controlled study after a 2-week placebo run-in period. This was a phase II clinical study carried out on out-patients in a single research centre. Fifteen elderly (63 +/- 10 years) hypertensive patients, without dementia but with memory complaints, were included. Psychomotor performance and cognition were assessed using both an extensive battery of validated psychometric tests (which evaluated attention and vigilance, body sway and memory) and an EEG profile. Cardiovascular parameters measured were blood pressure and heart rate. No detrimental effects of nicardipine were found on attention, vigilance, body sway or memory. Nicardipine produced a significant increase in alpha EEG energies, which may indicate possible alerting effects. In contrast, clonidine induced well-known deleterious sedative effects in psychometric tests and in EEG analysis (decrease in alpha and increase in delta and theta waves). The two drugs produced equivalent decreases in blood pressure at steady state. In conclusion, clonidine induced well-known sedative effects, while nicardipine did not impair central nervous system activity and may have had some short-term alerting effects in elderly hypertensive patients with memory complaints. This study supports the hypothesis of a dissociation between blood pressure and direct drug effects on the central nervous system.

Aims: Levocetirizine (R-cetirizine), is the active enantiomer of cetirizine, an antihistamine indicated in the treatment of allergic rhinitis and chronic idiopathic urticaria. The purpose of this trial was to analyse the effects of levocetirizine single and multiple doses on CNS using integrated measures of cognitive and psychometric performance., Methods: A battery of psychometric tests was used: critical flicker fusion (CFF), choice reaction time (CRT), body sway (BS), learning memory test (LMT) and subjective assessments of alertness compared with placebo. Nineteen (19) healthy male volunteers received either levocetirizine 5 mg (therapeutic dose), diphenhydramine 50 mg or placebo once daily for 5 consecutive days (3-way cross-over). Diphenhydramine was used as a positive control. CFF tests were performed on days 1 and 5 at baseline and up to 24 h following drug intake. Subjects used the Bond-Lader visual analogue scales (VAS) to assess their mood and vigilance., Results: In contrast to diphenhydramine, when compared with placebo, levocetirizine did not modify the CFF (primary endpoint), regardless of the dosing scheme (-1.62 Hz [-2.61, -0.64] and -0.81 Hz [-1.80, 0.19], respectively, 3 h after dosing on day 1). CRT was decreased with both levocetirizine and placebo up to 5 h after dosing on day 1 and up to 3 h after dosing on day 5. Body sway data were similar with levocetirizine and placebo but increased with diphenhydramine. LMT was similar in all three groups. No relevant difference between placebo and levocetirizine was recorded by the subjects on their assessment of alertness using the VAS, whilst decreased alertness was reported following diphenhydramine 50 mg., Conclusions: This study showed that levocetirizine does not produce any deleterious effect on cognitive and psychometric functions compared with placebo in healthy male volunteers.

Piribedil is a dopamine agonist acting on D2 and D3 central nervous system dopamine receptors. This drug has been administered to 12 young healthy male volunteers (age 22 +/- 2 years) according to a single center randomized, double-blind, two ways cross-over, placebo controlled trial, including a washout period of one week. Placebo and piribedil were administered by a single intravenous infusion over 2 h (3 mg). Psychomotor performance and cognitive functions were assessed through a standardized and computerized psychometric tests battery and a continuous electroencephalogram (EEG) mapping. Piribedil improved simple reaction time (P=0.02), immediate (P=0.045 and 0.004), and delayed free recall (P=0.05), dual coding test (P=0.02) and increased theta and fast beta waves on the EEG (P < 0.05 and 0.001, respectively). No deleterious effect was observed on the tests exploring attention and concentration via the other procedures. It is concluded that a single intravenous perfusion of piribedil 3 mg improves alertness and the information processing speed within the central nervous system, in healthy volunteers.

Tiapride is a substituted benzamide with selective dopamine D2 and D3-antagonist properties which appears to have preferential affinity for extra-striatal dopamine receptors. Tiapride is used in the treatment of agitation, aggressiveness and anxiety in the elderly. To define the effects of a single dose of tiapride 100 mg on psychomotor performance and cognitive functions and electroencephalogram (EEG), a randomized, double-blind, three-way crossover, placebo-controlled study using lorazepam 1 mg as a positive control was carried out in 12 elderly individuals (six women and six men, mean age +/- SD: 69 +/- 3 years). A 1-week wash-out interval was allowed between each administration. Psychomotor and cognitive functions were assessed using both objective [EEG, critical flicker fusion, simple reaction time, tapping, body sway, continuous performance task (CPT), digit symbol substitution test, Sternberg memory scanning and a learning memory test using word lists] and subjective (visual analogue scales) measures before and up to 6 h after dosing. Tiapride was devoid of any detrimental or sedative effects on EEG and all of the performance tasks used and did not impair memory compared with-placebo. In contrast, a single dose of lorazepam produced significant deleterious effects on psychomotor performance (decrease in tapping and in sustained attention (CPT) and an increase in reaction time and body sway), and sedative effects on EEG (significant increase in delta and decrease in alpha waves) as well as significant impairment in working memory (Sternberg) and anterograde amnesia (decrease in immediate and delayed free recall) up to 6 h after dosing compared with placebo and tiapride. In conclusion, the present study showed that in contrast to lorazepam 1 mg there is no evidence to suggest that a single dose of tiapride 100 mg has any sedative and amnestic effects in the elderly which may interfere with everyday life activities.

Amisulpride, a substituted benzamide, binds selectively to the dopamine D2- and D3-receptors. It has higher affinity for limbic compared to striatal dopamine receptors in vivo. At low doses, amisulpride facilitates dopamine transmission via a selective blockade of presynaptic D2- and D3-receptors. Amisulpride is an active antipsychotic compound effective at low doses for negative symptoms and at high doses for positive symptoms of schizophrenia. The CNS profile of multiple doses of a low dosage regimen of amisulpride (50 mg once daily for 4 days) was assessed in a randomised, double-blind, 3-way crossover, placebo-controlled study carried out in 12 young sleep-deprived (for 36 h) subjects, using EEG and various measures of psychomotor and cognitive functions. Caffeine slow release (600 mg) was used as a positive reference. Multiple doses of 50 mg amisulpride once daily were devoid of any detrimental effects on EEG and psychomotor performance and cognitive function after total sleep deprivation. In addition, 50mg amisulpride partially antagonized the deleterious effects of sleep deprivation on EEG and subjective sedation as shown by trends, and a significant increase in EEG relative beta power and a decrease in subjective sedation. These effects were more pronounced at the end of sleep deprivation, suggesting possible alerting effects of amisulpride at this dose level. Caffeine significantly antagonized the detrimental effects of sleep deprivation on vigilance (increase in EEG beta waves, speed of reaction, sustained attention and reduction in subjective sedation). In conclusion, the present results demonstrate that 50 mg amisulpride is devoid of detrimental effects on EEG, psychomotor and cognitive performance after sleep deprivation, a situation well-known to amplify such effects if they exist. Moreover, some data suggest possible alerting effects of this low dosage regimen of amisulpride.

Background: Patients with depression often have cognitive and psychomotor performance impairments. Antidepressive treatments can correct these deficits, provided sedative and anticholinergic adverse effects do not add to the preexisting condition, particularly in elderly patients. Newly developed antidepressants therefore should be without deleterious effects on cognitive functions, including memory. Befloxatone is a new antidepressant with a potent, selective, competitive, and reversible inhibitory activity on the A isoform of monoamine oxidase (MAO-A)., Methods: The effects on cognition and psychomotor performance of single oral doses of befloxatone (10 mg) and amitriptyline (50 mg) were compared in a randomized, double-blind, placebo-controlled, three-way crossover design trial in 12 healthy elderly (65 to 85 years) volunteers. The performances of the subjects were evaluated by a comprehensive battery of validated psychometric tests that explored alertness, psychomotor performance, information processing, and memory. Subjective feelings on mood and sleep were rated on visual analog scales. MAO-A inhibition was estimated by multiple titrations of 3,4-dihydrophenylglycol (DHPG) in plasma., Results: Amitriptyline displayed the expected deleterious effects on performance tasks, critical flicker fusion threshold, digit symbol substitution, and body sway, and it deteriorated memory (immediate and delayed free recall of words). In contrast, befloxatone did not impair cognition or psychomotor performance but instead significantly improved the delayed free recall. Amitriptyline adversely affected subjective feelings of alertness and contentedness, but befloxatone permitted sustained alertness and did not alter other subjective feelings or sleep. Concurrently, a single dose of 10 mg befloxatone markedly decreased the DHPG concentration in plasma., Conclusion: Contrary to tricyclic antidepressants, whose deleterious effects are greater in elderly subjects, this study demonstrated the safety of befloxatone on cognition and psychomotor performance in elderly subjects.

Recent data obtained in animals and in humans suggest that both MAO-A and MAO-B inhibitors present cognitive enhancing properties of possible interest in the treatment of cognitive disorders. In addition, the rational for using selegiline as a neuroprotector in Parkinson's disease may also be applicable in Alzheimer's disease in which a dramatic increase in the MAO-B activity has been reported. It seems then worthwhile to investigate the neuroprotective effect of MAOIs in humans and to assess, furthermore, the real therapeutical benefit of their cognitive enhancing properties.

The respective effects of three antidepressant drugs (moclobemide, 450 mg/j; viloxazine, 300 mg/j; maprotiline, 150 mg/j) on vigilance, attention, and memory were compared. Young depressed outpatients (n = 46) entered a double-blind, randomized, monocentre clinical trial lasting for 6 weeks. Drug actions were assessed through the regular determination of critical flicker fusion point (CFF), reaction times (SRT), and a battery to measure memory components. None of the three drugs caused deterioration in cognitive functions. On the other hand, moclobemide improved both vigilance and attention (CFF, SRT) and some crucial components of memory (general memory scores, delayed word recall, recognition of familiar faces). This effect was rapid, stable, and superior to those of viloxazine and maprotiline. It may be explained by moclobemide's selective and reversible inhibition of monoamine oxidase A, as well as by the lack of any anticholinergic action.