Lack of effect of single and repeated doses of levocetirizine, a new antihistamine drug, on cognitive and psychomotor functions in healthy volunteers.

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.

Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients.

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.

Effects of 50mg amisulpride on EEG, psychomotor and cognitive functions in healthy sleep-deprived subjects.

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.

Effects of tiapride on electroencephalograms and cognitive functions in the elderly.

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.

Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease.

BACKGROUND: Silymarin is a well-known hepatoprotective agent. Tacrine, the first drug marketed for Alzheimer's disease (AD), induces an elevation of serum liver transaminase prohibiting an effective dosage in many patients. This 12-week randomised, double-blind, placebo-controlled study was undertaken to evaluate the ability of silymarin to antagonise or prevent the hepatotoxic effects of tacrine and to analyse its action on tacrine efficacy and tolerability. METHODS: Outpatients suffering from mild-to-moderate dementia of the Alzheimer type were randomly assigned to two treatment groups: tacrine + silymarin and tacrine + placebo. The study was double-blind for silymarin and open for tacrine and was conducted in 22 French neurology and geriatric centres. Silymarin (420 mg/day) was given first (1 week) and tacrine was added at 40 mg/day for 6 weeks, then increased to 80 mg/day (6 weeks). Serum ALAT was the main evaluation criterion (> upper limit of normal, ULN). Serum ASAT as well as adverse side effects and cognitive performance assessed by MMSE and the Syndrome Kurtz test (SKT) were secondary evaluation criteria. Null hypotheses were evaluated with Fisher's exact test. FINDINGS: 222 patients were recruited and received silymarin and tacrine (110 patients) or placebo and tacrine (112 patients). 28 patients dropped out; 217 were included in the intent-to-treat analysis. No statistical difference was observed between the two groups for serum ALAT (p = 0.39). Fewer patients had ALAT levels >5 ULN in the silymarin group (-33.3%). Side effects and notably gastrointestinal disorders were much less frequent in the silymarin group. Cognitive performance remained unchanged in both groups. INTERPRETATION: Silymarin does not prevent tacrine-induced ALAT elevation but does reduce the rate of gastrointestinal and cholinergic side effects without any impact on cognitive status. As a consequence, silymarin (420 mg/day) could be co-administered with tacrine to improve tolerability in the initial phases of AD treatment.

Cognitive performance in elderly subjects after a single dose of befloxatone, a new reversible selective monoamine oxidase A inhibitor.

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.

Effect of bromazepam versus placebo on inhibition and waiting capacity in young women with traits of anxiety.

The effect of 3 dosages of bromazepam administered as single oral doses (1.5, 3 and 6 mg) on anxious inhibition phenomena was studied in a population of 16 young women (18-30 years) with anxiety-traits, selected on the criteria of Cattell's anxiety scale supported by two personality inventory (Eysenck's, MMPI). A double-blind, placebo study design was chosen. The main assessment criteria were based on the go/no-go test (Logan's procedure), slow response rate (SRR) and a task of forced or unforced decision (use of the CFF). Attentional processes and declarative memory were analyzed as secondary criteria. None of the three dosages modified inhibition or acting-out. Sustained attention was reduced with 1.5 mg and 6 mg, as was memory performance with 3 and 6 mg, 3.5 h after drug administration. In contradistinction with studies carried out in healthy volunteers or with other benzodiazepine compounds, bromazepam at single low dosages does not modify inhibition capacity in these subjects with traits of anxiety, in this particular procedure.

Antidepressant-like effects of alnespirone (S 20499) in the learned helplessness test in rats.

The effects of the new chroman derivative, alnespirone (S 20499), which is a selective 5-HT1A receptor agonist, were investigated in an animal model of depression, the learned helplessness test. Rats previously submitted to a session of 60 inescapable electric foot shocks (learned helpless controls) exhibited a deficit in escape performance in three subsequent shuttle-box sessions. Alnespirone was administered twice daily via the oral route (2.5, 5, 10, 20 mg kg(-1) day(-1)). It was shown to protect against the elevation in escape failures caused by exposure to the uncontrollable aversive situation at 5 and 10 mg kg(-1) day(-1) p.o. (13+/-2 and 10+/-3 escape failures, respectively, vs. 9+/-2 escape failures in control rats). In addition, alnespirone had a tendency to elevate the number of intertrial crossings during the resting periods, depending on the dose and day on which the avoidance task was performed (15+/-2 intertrial crossings at the dose of 5 mg kg(-1) day(-1), vs. 5+/-2 intertrial crossings for the helpless control rats, on the second day). In comparison, imipramine (64 mg kg(-1) day(-1) p.o.) provided marked protection on all three days of the avoidance task and tended to increase the number of intertrial crossings during the resting periods on the second and the third days. It is concluded that alnespirone exerts antidepressant-like properties in the learned helplessness test in rats, in a manner similar to 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), buspirone and ipsapirone, other 5-HT1A receptor agonists.

Absolute bioavailability and electroencephalographic effects of conventional and extended-release formulations of venlafaxine in healthy subjects.

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.

[Baseline blood pressure in healthy normotensive volunteers]. / Etat basal de la pression artérielle chez le volontaire sain normotendu.

UNLABELLED: The aim of this study was to define the reproducibility and the time required to obtain a stable baseline level of blood pressure (BP) in normotensive volunteers during a phase I trial. Blood pressure was recorded automatically (Dinamap and Marquette monitors) every 5 min during a 2-hour period and manually (Random zero device) at T20, T60 and T120, twice at a one-week interval, under similar study conditions (6 in the morning, 7 in the afternoon) in supine position in 13 normotensive men (aged 20 to 28). The average BP was compared using a 3-way ANOVA (subject, time, week). 1.SBP/DBP decreased significantly (p < 0.001) from one week to the other and SBP, but not DBP, decreased significantly over time up to T75 (p < 0.001): [table: see text] 2. SBP was significantly higher in the morning than in the afternoon during both weeks (p = 0.001). The decrease in SBP with rest was only observed in the morning (p = 0.00001). 3. Reproducibility and change over time and period did not significantly differ between manual and oscillometric methods. The best reproducibility of T75 was obtained with the mean of 3 automatic values (T70, T75, T80). CONCLUSION: in normotensive subjects, BP decreased from one period to the next and with rest. The baseline value of BP was obtained from T75 with the best reproducibility when baseline BP level is defined by 3 automatic values.

Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria.

OBJECTIVE: To evaluate the efficiency of mitoxantrone in multiple sclerosis. METHODS: Forty two patients with confirmed multiple sclerosis, selected as having a very active disease on clinical and MRI criteria were randomised to receive either mitoxantrone (20 mg intravenously (IV) monthly) and methylprednisolone (1 g iv monthly) or methylprednisolone alone over six months. In the steroid alone group five patients dropped out due to severe exacerbation. RESULTS: Blinded analysis of MRI data showed significantly more patients with no new enhancing lesions in the mitoxantrone group compared with the steroid alone group, (90% v 31%, P < 0.001). In the mitoxantrone group there was a month by month decrease almost to zero in the number of new enhancing lesions, and in the total number of enhancing lesions, whereas both remained high in the steroid alone group. The differences were significant for both indices at all months from 1-6. Unblinded clinical assessments showed a significant improvement in change in EDSS at months 2-6 in the mitoxantrone group, with a final mean improvement of more than one point (-1.1 v + 0.3; P < 0.001). There was a significant reduction in the number of relapses (7 v 31; P < 0.01), and an increase in the number of patients free of exacerbation (14 v 7; P < 0.05). CONCLUSION: In this selected group of patients with multiple sclerosis with very active disease, mitoxantrone combined with methylprednisolone was effective in improving both clinical and MRI indices of disease activity over a period of six months whereas methylprednisolone alone was not. Further double blinded long term studies are needed to properly evaluate the effect of mitoxantrone on progression in disability.

Drugs used in Alzheimer's disease and neuroplasticity.

Drugs indicated for use in Alzheimer's disease (AD) must clinically improve the cognitive symptomatology of the disorder, although nonexclusively. From a neurochemical standpoint, these drugs must oppose the multiple processes recognized as stigmata of AD. In these two ways, so-called AD drugs may be considered substances modifying cerebral plasticity. Long-term evaluation of anticholinesterases and of tacrine, in particular, provides arguments in support of this initially purely biologic, theoretical approach. This concept of neuroplasticity applied to dementia may modify the traditional pharmaceutical drug development programs.

Systemic and regional hemodynamic and biological effects of a new kappa-opioid agonist, niravoline, in healthy volunteers.

We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular system, on diuresis and on plasma and urinary osmolalities and electrolytes. This was a placebo-controlled, randomized, double-blind, crossover study performed in 12 healthy volunteers. Compared with placebo, niravoline induced a significant, early and potent diuresis, which peaked within 2 hr (urine output increased 2.4-fold) and lasted for 4 hr. Niravoline significantly decreased, between 0 and 2 hr, urine osmolality (-71%) and sodium (-38%) and potassium (-29%) excretion and significantly increased plasma osmolality and natremia, without changing kalemia. Niravoline induced a slight, but significant, increase in blood pressure (+8% at 0.5 hr), which disappeared within 2 hr. Because heart rate, stroke volume and cardiac output were not modified, this effect was due to an increase in total peripheral resistance (+22% at 0.5 hr). Niravoline did not modify brachial artery diameter and flow and corresponding vascular resistance. Niravoline tended to decrease plasma vasopressin levels and urinary excretion and significantly increased plasma levels of norepinephrine (+44% at 0.5 hr), active renin (+22% at 1.25 hr), aldosterone (+52% at 1.25 hr) and atrial natriuretic factor (+20% at 2 hr). We conclude that niravoline induces a potent aquaretic effect associated with antinatriuresis and antikaliuresis. These main effects are accompanied by a stimulation of the sympathetic and reninangiotensin systems and a slight and transient increase in blood pressure.

[Study of correlations between self-estimation of memory, psychometric test (SM9) and test of memory in daily life]. / Etude de correlations entre autoestimation de la mémoire, test psychométrique (SM9) et test de mémoire de la vie quotidienne.

Assessment of memory performance is now well established. However, the normal form of assessment does not evaluate memory problems encountered during daily activities, a situation relevant to the evaluation of drug effects on memory components. The present study examines the ecological validity of psychometric tests. 49 individuals, from 20 to 89 years old without any identified pathology were included in the study, with the aim of establishing correlations between an autoquestionnaire of memory, a standard memory battery (SM9) and a daily memory video test (DMV). No correlation was found between self-estimation and objective tests or DMV. A strong correlation (r = 0.81) was found between SM9 and DMV. Imaged information and verbal coding appear to be essential parameters of objective tests. These results confirm the ecological validity of the objective psychometric tests and in particular of SM9.

[Randomized double-blind comparative study of minaprine (200mg/j) and of placebo on memory loss]. / Etude comparative en double aveugle randomisée de la minaprine (200 mg/j) et du placebo sur la plainte mnésique.

Thirty five subjects (age: 45-69 years) with subjective memory loss, without any other neuropsychiatric or somatic disease, were recruited in a phase II study. This double blind randomized versus placebo controlled study compared the effects of minaprine (200 mg/d) with placebo, in two parallel groups, during 2 months, on memory, attention and vigilance. Three psychometric tests were the main criteria of assessment: a standardized battery of memory tests (SM 5), the dual-coding test, the analysis of choice reaction times (CRT) and the critical flicker fusion point (CFF). A positive effect of minaprine was detected on words delayed recall (p = 0.028) and immediate recognition of words (p = 0.049). The global clinical tests (CGI, MacNair scale) were not statistically modified. Tolerability of minaprine and placebo were comparable. A positive pharmacodynamic activity on mnemonic performance is thus demonstrated in favour of minaprine (200 mg/d) in this specific population characterized by a memory complaint. These results would lead to a phase III study in which the main criteria would be global scales in order to confirm the clinical reliability of the present results.

Pharmacodynamics and pharmacokinetics of two dose regimens of befloxatone, a new reversible and selective monoamine oxidase inhibitor, at steady state in healthy volunteers.

The pharmacodynamic equipotency of 2 dose regimens (5 mg twice daily versus 10 mg once daily) of befloxatone, a new reversible and selective monoamine oxidase A (MAO-A) inhibitor, after single and multiple doses for 6 days was examined in a randomized, double-blind, three-way crossover, placebo-controlled trial of 12 healthy volunteers. Plasma levels of the deaminated metabolite 3-4 dihydroxyphenylglycol (DHPG), as measured by high-performance liquid chromatography (HPLC) with coulometric electrochemical detection, were used as an index of MAO inhibition. A single dose of befloxatone produced a significant dose-related reduction in plasma DHPG levels, as shown by the decrease in the 24-hour area under the concentration-time curve (AUC0-24) of DHPG, which peaked 2 hours after administration and persisted over 24 hours. Both dose regimens provided equipotent extent and duration of MAO-A inhibition at steady state, suggesting a once daily dosage should be sufficient for most patients. The pharmacokinetic bioavailability at steady state of both dose regimens was also similar. The concentration-time effect curve after a single dose revealed a hysteresis corresponding to the delay necessary to elicit MAO inhibition and/or elimination of DHPG. The relationship between plasma levels of DHPG and/or elimination of plasma concentrations of DHPG and befloxatone after a single dose can be modeled using the Emax model with a mean EC50 of 4.75 ng/mL, and suggests the presence of a maximal response from the single dose. This model permits prediction of steady-state levels of DHPG.

Procedural memory and Parkinson's disease.

A detailed analysis of the mnestic deficits associated with Parkinson's disease (PD) contributes to explaining the cognitive disorders and their well documented consequences. This study was designed to show that, in PD declarative as well as procedural memory is severely impaired. Three tests designed to explore this aspect of mnestic functioning were proposed to a group of 16 parkinsonian patients whose motoricity was controlled: inverted reading, braille reading, sound form association. The results obtained, compared with those of young and aged controls, show that PD is associated with marked deficits in both declarative and procedural memory. Declarative memory impairment was similar to that observed in the control population (healthy elderly subjects, age-matched with the PD patients) but more marked in PD subjects. The procedural memory deficit was linked with age and pathology. Procedural memory involves a variety of processing modules dedicated to the type of information (visual, auditive, tactile codes). The deficits observed were more like a loss of automatism than procedural impairment stricto sensu ('knowing how'). It would be worth pursuing research by studying akinesia and motor disorders from the angle of automatic memory impairment.

Explicit and procedural memory in Parkinson's disease.

One of the aims of cognitive psychology is to breakdown complex tasks into their most basic components. The components of explicit (declarative) and implicit (procedural) memory were thus analyzed in undemented, non-depressed Parkinsonian patients under anti-Parkinsonian treatment, and compared with young and elderly healthy subjects. Three series of experiments were conducted in 61 patients in total. Statistically significant results revealed an impairment of explicit memory (verbal recall of words and drawings) with preserved recall of faces, in Parkinsonians. Implicit memory was also deficient, only in association tests (sound-form; arithmetical alphabet) and maze tests. Braille reading tests and Toronto tower tests did not discriminate between Parkinsonians and elderly subjects. Lastly, analyzing learning and automation revealed a dysfunctioning in Parkinsonian patients. All these data indicate a dysregulation of the cortical-sub-cortical systems, not essentially pre-frontal, and not necessarily dopaminergic. Cognitively, it appears that procedural and implicit memories should be dissociated conceptually.

Monoamine oxidase inhibitors, cognitive functions and neurodegenerative diseases.

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.