Biomedical subjects

D Bentué-Ferrer

Publications and source records attributed to D Bentué-Ferrer.

At least 19 recordsLinked to original sources

PubMed2006

Effect of training and detraining on catecholamine responses to sprint exercise in adolescent girls.

Training is well known to influence catecholamine responses to exercise. In women, this training effect is still not well characterized and has been studied mostly in adults. Hence, we investigated in this longitudinal study, the effects of a 6-month sprint training program followed by 5 months of detraining on plasma catecholamine responses to a sprint exercise in young female subjects. Twelve healthy adolescent girls [training group (TG), n=6; control group (CG), n=6] took part in our study. TG participated in 6 months of supervised sprint training program (3 days/week) and has no training past whereas, CG continued with it's normal activity. A 6s-sprint test was performed on a cycle ergometer before training (P1) and after training (P2) in both the groups. TG only realized a 6s-sprint test after 5 months of detraining (P3). Blood lactate concentrations (La) as well as plasma adrenaline (A) and noradrenaline (NA) concentrations were measured at rest, immediately after the warm-up and the 6s-sprint and during recovery. Peak power W peak), expressed both in absolute and relative values, were significantly increased in TG in P2 (P<0.01) but did not change in CG. After the sprint-training period, the warm-up and the 6s-sprint induced plasma A increase and the maximal A concentrations were significantly higher than in P1 and P3 for TG only (P<0.05). Plasma A did not change in CG after 6 months. In P3, W peak and maximal lactate concentrations ([La]max) were significantly greater compared to P1 and P2 in TG (P<0.05). In CG, [La]max were significantly increased in P2 (P<0.05). The present study demonstrates that 6 months of sprint training in adolescent girls induce both an increase in performances and in A responses to sprint exercise. This adrenergic adaptation disappears after 5 months of detraining whereas the gain in performance is maintained. These new data may lead to practical considerations.

Adaptation, Physiological↗

PubMed2004

[Myoclonic encephalopathy associated with proton pump inhibitors].

Two men (66 and 73 Years) with a cardiovascular history were hospitalized for rapid onset encephalopathy associated with myoclonia and an extrapyramidal syndrome. On the basis of the French Pharmacovigilance system, this symptomatology has been attributed to the coadministration of a proton pump inhibitor, lansoprazole (15mg/day) with levodopa. Lansoprazole withdrawal led to a normalisation of the situation.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

[NOEMIE: an epidemiological study of migraine at work: results from 17 occupational health centres].

INTRODUCTION: A survey (NOEMIE, Nouvel Observatoire Epidemiologique de la Migraine en Entreprise) was carried out in France in 17 occupational healthcare units in order to identify subjects suffering from migraine headache with the aim of guiding them towards a healthcare program. The data collected in the participating units are presented. METHODS: and patients. NOEMIE was a national cross-sectional, observational, multicentric study with a 6-month follow-up. Two groups of migraine sufferers (according to IHS criteria) were included and divided into two groups: subjects already managed for their migraine (group A) and subjects who had not sought healthcare for migraine for more than 12 months (group B). The main objective was to evaluate changes in the quality-of-life score (QVM) 6 months later. RESULTS: At inclusion, the two groups were comparable for demographic features, history of migraine, and disease severity. A significant difference was observed between the two groups for frequency of attacks, disease management, and evaluation of treatment efficacy and of quality-of-life. At 6 months, patient satisfaction and quality-of-life were significantly improved (6 to 10 point improvement). For the 4753 reported attacks, 12.4 percent of the patients in group A required sick leave versus 10.9 percent in group B. Frequency of sick leave was considerably improved in both groups. CONCLUSION: By identifying subjects suffering from migraine headache who had not sought specific medical care and advising them to seek medical management, the employee healthcare units improved the subjects' quality-of-life, promoted adequate medical management and reduced occupational consequences of migraine headache.

Adult↗

PubMed2002

Effects of risperidone on psychometric and cognitive functions in healthy elderly volunteers.

RATIONALE: Dementia includes not only cognitive deficit but may also include psychiatric and behavioral symptoms. These psychological symptoms of dementia require specific treatment without deleterious effects on cognitive functions. OBJECTIVE: The aim of the present study was to assess the effects of a single dose of risperidone (0.25 or 0.5 mg) on psychomotor performances and cognitive functions compared to a placebo and to a positive control, lorazepam 1 mg, in 12 healthy elderly subjects. METHODS: This study was a randomized, double-blind, four-way crossover clinical trial involving four 8-h long treatment periods. The pharmacodynamic assessment criteria included a battery of psychomotor tests, a subjective evaluation and an electroencephalogram. Safety was evaluated by clinical laboratory tests, electrocardiogram and recording of adverse events. Concentrations of risperidone, 9-hydroxy-risperidone and lorazepam were determined before and 2 h after dosing. RESULTS. Few significant effects were observed on psychomotor tests with risperidone at all dosages. Risperidone was devoid of any deleterious effects on speed of reaction, vigilance and sustained attention, working and long-term memory and increased cortical arousal. Risperidone demonstrated minor impairment on motor activity (decreased finger taping), postural stability, and information processing (impaired digit symbol substitution). Contentedness subjective evaluation was decreased with risperidone 0.5 mg, 6 h after dosing. No significant difference was observed on EEG frequencies and no sedative activity was detected with risperidone. At 2 h after dosing, risperidone plasma concentrations were 1.54+/-0.99 ng/ml and 2.80+/-1.41 ng/ml; 9-hydroxy-risperidone concentrations were 0.77+/-0.46 ng/ml and 1.54+/-0.85 ng/ml after intake of 0.25 mg and 0.5 mg doses, respectively. Well-known detrimental effects of lorazepam on psychomotor performances were observed and sedative effects were confirmed by the EEG findings. At 2 h following lorazepam 1 mg administration, plasma concentrations were 13.40+/-2.17 ng/ml. None of both compounds induced serious adverse events. CONCLUSION: The results of this clinical trial conducted on healthy subjects demonstrated that low doses of risperidone, but not low doses of lorazepam, did not disturb the cognitive functions in the elderly.

Aged↗

PubMed2002

[Effect of almitrine/raubasine on cerebral metabolism in the elderly].

Recent neurobiological data has led to renewed interest in oxygen (O2). The discovery of neuroglobin, protein varyingly present in the brain, has been enhanced by the elucidation of the mechanisms through which oxygen intervenes in neuronal metabolism. Almitrine/raubasine activates the metabolism of hypoxic/ischemic neurones by increasing O2 bioavailability. This mechanism supports the effects on behaviour obtained in various animal models and the benefits observed during clinical trials in elderly patients presenting with cognitive defects.

Aged↗

PubMed2002

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.

Aged↗

PubMed2002

Training status (endurance or sprint) and catecholamine response to the Wingate-test in women.

The aim of this study was to verify if, as for men, training status induces different catecholamine responses to exercise. To do this, we investigated the effect of training status (sprint or endurance) on plasma catecholamine response to a supramaximal exercise in women. Nineteen subjects took part in our study: six untrained subjects (UT), seven endurance trained subjects (ET) and six sprint trained ones (ST). The trained subjects (ET and ST) were all competing at a high national level. The maximal power (W max ) and the mean power (W) were determined from the Wingate-test. Blood lactate, adrenaline (A) and noradrenaline (NA) were analysed at rest (La 0, A 0 and NA 0 ), immediately at the end of the exercise (A max and NA max ) and after 5 min recovery (La max [3 min in arterialized blood], A 5 and NA 5 ). The disappearance of A and NA was judged by the ratio (A max -A 5 )/A max and (NA max -NA 5 )/NA 5. The ratio A max /NA max was considered as an index of the adrenal medulla responsiveness to the sympathetic nervous activity. As expected, during the Wingate-test ST exhibited significantly higher performances compared to UT and ET. But in contrast to the men's data no difference was observed between the three groups both for La max (13.1 +/- 0.8 mmol x L (-1); 14.8 +/- 1.0 mmol x L (-1) and 11.2 +/- 0.5 mmol x L (-1) respectively for ET, ST and UT), NA max (22.1 +/- 1.2 nmol x L (-1); 13.1 +/- 2.4 nmol x L (-1) and 20.2 +/- 7 nmol x L (-1)respectively for ET, ST and UT) and A max (4.1 +/- 0.8 nmol x L (-1); 2.6 +/- 0.6 nmol x L (-1); 13.1 +/- 0.6 nmol x L (-1) respectively for ET, ST and UT). Consequently the ratio A max /NA max was similar in UT, ET and ST (respectively 0.2 +/- 0.03; 0.2 +/- 0.04; 0.17 +/- 0.04), These results indicated, in contrast to the men's data, that the catecholamine response to the Wingate-test did not differ between female subjects of different status of training. In conclusion this study did not find any significant effect of training status on the catecholamine response to supramaximal exercise and so argues in favour of sex differences in response to training.

Adult↗

PubMed2001

Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam.

Several recent studies have demonstrated that alprazolam and lorazepam, administered at low doses to healthy volunteers, improve cognitive functions and psychomotor performances. Paradoxical effects of low-dose benzodiazepines have been also observed in mice, in experimental pharmacology. The aim of this work was to determine, in rat, the effect of similar low-doses of benzodiazepines on spontaneous locomotor activity and performance in the elevated zero-maze, and to investigate the underlying neurobiological mechanisms. The dose-effect and the time-course of the action were studied for both compounds. Spontaneous locomotor activity was measured using a photoelectric actimeter. The level of anxiety of the animals was assessed in the elevated zero-maze. Dopamine, serotonin, and their metabolites were assayed in the extracellular striatal fluid of the awake rat, obtained by microdialysis, by HPLC--EC. Spontaneous locomotor activity observed in rats given low-dose alprazolam and lorazepam evidenced a stimulatory effect only with alprazolam. The effect was maximum 90 min after administration of 0.0050 mg/kg alprazolam. An anxiogenic-like action was evidenced with the elevated zero-maze for the two compounds. We observed a statistically significant increase in striatal dopamine concentrations only with alprazolam, during the period corresponding to the behavioral stimulatory effects. We also showed a marked trend towards increased levels of serotonin with alprazolam but this modification was not significant, in spite of statistically significant variations of 5-HIAA. In the rat, behavioral stimulatory effects of low-dose benzodiazepines is evidenced with alprazolam but not lorazepam. This effect could be explained, at least in part, by increased extracellular dopamine concentrations in the striatum. Their different structures could explain the different pattern observed for the two benzodiazepines.

Alprazolam↗

PubMed2001

Effect of training status on the sympathoadrenal activity during a supramaximal exercise in human.

BACKGROUND: The study investigated the concentrations of plasma catecholamine, adrenaline (A) and noradrenaline (NA), and the adrenal medulla responsiveness to the sympathetic nervous activity in sprinters (S), endurance runners (E) and untrained subjects (U) during a supramaximal exercise (the Wingate-test). METHODS: A group of 19 men took part in the tests: 6 S (20.5+/-0.7 years), 6 E (21.0+/-1.0 years) and 7 U (20.9+/-0.4 years). The maximal power (Wmax) and the mean power (W) were determined from the Wingate-test on a cycle ergometer. The plasma lactate, A and NA were analysed at rest (La0, A0 and NA0), immediately at the end of the exercise (Amax and NA(max)) and after 5 min recovery (La(max), A5 and NA5). The disappearance of A and NA was judged by the difference between the maximal values and those determined after 5 min recovery (Amax-A5 and NA(max)-NA5) and the ratio A/NA was considered as an index of the adrenal medulla responsiveness to the sympathetic nervous activity. RESULTS: During the Wingate-test S exhibited higher performances and higher La(max) than the two other groups. At the end of the Wingate-test the NA(max) values were similar in the three groups whereas the Amax values were significantly higher in S than in E and U (8.00+/-0.5 nmol x l(-1) in S vs 3.47+/-0.30 nmol x l(-1) and 3.29+/-1.14 nmol x l(-1) respectively in E and U). This leads to a higher Amax/NA(max) ratio for S compared to the other two groups (0.77+/-0.10 in S vs 0.23+/-0.03 and 0.28+/-0.05, respectively in E and U). As the disappearance of A (Amax-A5) was significantly higher in S (6.80+/-0.47 nmol x l(-1) in S vs 2.64+/-0.19 nmol x l(-1) and 1.64+/-1.37 nmol x l(-1), respectively in E and U), the higher values of Amax in S could be explained by an increase of the adrenal medullary secretory capacity in this group. CONCLUSIONS: It was concluded that essentially short term and intense exercises as sprint ones or interval-training may alter the adrenal medulla responsiveness to supramaximal exercise but not long duration exercises.

Adrenal Medulla↗

PubMed2000

Five-year follow-up of early lisuride and levodopa combination therapy versus levodopa monotherapy in de novo Parkinson's disease. The French Lisuride Study Group.

The value of an early initial coadministration of levodopa (L-dopa) and lisuride in Parkinson's disease was the main goal of the present study. Eighty-two patients with recently diagnosed idiopathic Parkinson's disease were randomized into two groups for treatment with L-dopa alone or L-dopa + lisuride. The trial was double-blinded for the first year and open for the following 4 years. Selegiline (10 mg/day b.i.d.) was added in both groups at the end of the first year. Outcome measures were evolution of L-dopa dosage and Unified Parkinson's Disease Rating Scale scores and subscores, and incidence of motor complications. The dropout rate was higher in the L-dopa group (63.4%) than in the combination group. Motor improvement was better (p < 0.01) in the L-dopa + lisuride group. Expected motor complications were rare, moderate and equivalent in the two groups despite a difference in L-dopa dosage (446.7 vs. 387.5 mg/day). Long-term follow-up demonstrated the L-dopa-sparing effect of lisuride (average 1 mg/day), the beneficial effect of early combination therapy on motor status and the paucity of motor complications in both groups.

Adult↗

PubMed2000

[The physiopathology of migraine].

Although the neurobiological causative factors are now beginning to be understood, to a large extent the complex mechanisms involved in migraine remain an enigma, with the appearance of a transient unilateral cephalic pain, possibly preceded by a protean aura and associated with several other symptoms. The factors involved include three clinical signs or symptoms, i.e., pain, the aura (focalized neurological and neurosensory signs), and accompanying symptoms (e.g., sensory, psychological, or digestive); and three anatomical sites, i.e., the brain, the meningeal or intracranial vessel and a peripheral cranial nerve, the trigeminus (V). Familial hemiplegic migraine (FHM) has led to a consideration of the genetic origin of ionic channel-dependent pathologies (channelopathies), while certain other arguments which are for the most part indirect favor the hypothesis of abnormalities, again possibly of genetic origin, in the central neurotransmitters (including serotonin), which are involved in the transmission of pain messages and in vasomotor control. However, the main point is that each of the sites involved has its specific pharmacopoeia, which can contribute towards the treatment of migraine.

Humans↗

PubMed1999

[Beta interferon in multiple sclerosis: pharmacological differences].

Interferons beta (INF) would be a good recombinant therapeutic choice for the management of relapsing remitting multiple sclerosis (RRMS). Three forms are approved in various countries including one IFN beta-1b (Betaféron) and two IFN beta-1a (Avonex and Ribif). These agents are apparently similar although they are not identical. Differences may be of clinical relevance. Important differences are described here in terms of pharmacokinetics, the spectrum of side effects and molecular chemistry. The clinical consequences on the benefit/risk ratio are discussed. This review recalls the difficulty in developing such compounds and in reaching marketing approval. An improvement in the acceptability and efficiency of IFN beta could by obtained when analyzing basic research data.

Adjuvants, Immunologic↗

PubMed1998

5-HT-moduline, a 5-HT(1B/1D) receptor endogenous modulator, interacts with dopamine release measured in vivo by microdialysis.

5-Hydroxytryptamine-moduline (5-HT-moduline) is an endogenous tetrapeptide (Leu-Ser-Ala-Leu) recently isolated and characterized from mammalian brain. This compound interacts with 5-HT1B receptors as a non-competitive, high-affinity antagonist and has the properties of an allosteric modulator. 5-HT-moduline could play an important role in the regulation of serotonergic transmission and also, through heteroreceptors, dopaminergic transmission. The aim of this work was to examine the potential ability of 5-HT-moduline to modify the basal extracellular concentration of dopamine and its metabolites (3-methoxytyramine, dihydroxyphenylacetic acid and homovanillic acid), in the rat striatum and to determine its potential interaction with the stimulating activity of a specific 5-HT1B receptor agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl) pyrrolo [3,2-b] pyrid-5-one (CP-93,129), on the release of dopamine. The technique is based on in vivo microdialysis using probes implanted in the striatum of the conscious rat. Results showed that the perfusion of 5-HT-moduline directly into this structure (1.25 mM) increased the striatal level of dopamine by two-fold (104% of the absolute basal release values, P = 0.0015) and that of 3-methoxytyramine by 3-fold (293%, P = 0.0001) without any change in the terminal metabolite concentrations. The intrastriatal administration of CP-93,129 induced a statistically significant, dose-dependent increase of dopamine levels (P < 0.0001). Coperfusion of 5-HT-moduline did not significantly alter the effect of CP-93,129 at 0.1 and 0.5 mM, but appeared to have an additive effect on the lowest dose (P = 0.0406). The results obtained show that 5-HT-moduline directly administered into the striatum increases the release of dopamine in this area. Presumably, this effect results from the desensitization of 5-HT1B receptors located on dopamine terminals. However, the fact that a 5-HT1B receptor agonist (CP-93,129) also increased the release of dopamine in the striatum and that 5-HT-moduline exhibited a slight additive effect with that of a low concentration of CP-93,129 suggests that the two substances interact with different mechanisms.

Animals↗

PubMed1998

Dopamine D2 receptor agonists protect against ischaemia-induced hippocampal neurodegeneration in global cerebral ischaemia.

To characterise the role played by dopamine receptors in ischaemic brain damage, we have evaluated the effects of pergolide, bromocriptine and lisuride (dopamine D2 receptor agonists), haloperidol (a dopamine D2 receptor antagonist), 2,3,4,5-tetrahydro-7,8,dihydroxy-1-phenyl-1H-3-benzazepine (SKF 38393; a dopamine D1 receptor agonist) and (R)-(+)-8-chloro 2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SCH 23390; a dopamine D1 receptor antagonist) in the gerbil model of global cerebral ischaemia. Ischaemia was induced by 5 min of bilateral carotid artery occlusion under halothane anaesthesia. Sham operated animals were used as controls. Pergolide (0.5 or 1.0 mg/kg i.p), bromocriptine (0.5 or 1.0 mg/kg i.p.), lisuride (0.5 or 1.0 mg/kg i.p.), SCH 23390 (0.1 or 1.0 mg/kg i.p.), haloperidol (0.5, 1.0 or 2 mg/kg i.p.) and SKF 38393 (1.0 or 2 mg/kg i.p.) were administered 1 h before occlusion. Five-minute-occluded animals had extensive damage in the CA1 region of the hippocampus 5 days after surgery. Pergolide 0.5 and 1.0 mg/kg i.p. provided significant (P < 0.05 and P < 0.01, respectively) neuroprotection against the ischaemia-induced hippocampal damage. Bromocriptine and lisuride also provided significant (P < 0.05) neuroprotection, but only at the higher 1.0 mg/kg dose. In contrast, the dopamine D2 receptor antagonist (haloperidol), the dopamine D1 receptor agonist (SKF 38393) and the dopamine D1 receptor antagonist (SCH 23390) failed to provide any neuroprotection in the model. These results support studies indicating that dopamine is important in ischaemic situations. The results also indicate that dopamine D2 receptor agonists are neuroprotective against ischaemia-induced brain injury and may play a role in neurodegenerative disorders.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1998

Adrenal medulla responsiveness to the sympathetic nervous activity in sprinters and untrained subjects during a supramaximal exercise.

The purpose of this study was to compare the adrenal medullar responsiveness to the sympathetic nervous activity between sprinters and untrained subjects after a supramaximal exercise (Wingate-test). Thirteen subjects took part in this study: 7 male athletes (20.3+/-1.8 years) competing in sprint running (S) and 6 untrained men (UT) (21+/-1.3 years). They performed an incremental treadmill test to determine the maximal oxygen uptake (VO2max), a force-velocity test and a Wingate-test on 3 different days, separated by a maximal interval of 15 days. The maximal power (Wmax) and the mean power (W) were determined from the Wingate-test on a cycle ergometer. Plasma lactate, adrenaline and noradrenaline concentrations were determined at rest (La0, A0, NA0), immediately after the Wingate-test (Amax, NAmax) and after 5 minutes recovery (Lamax, A5 and NA5). S exhibited higher performances than UT during the Wingate-test as shown by their significantly higher values of Wmax (1111+/-38 w in S vs 886+/-148 w in UT), W (822+/-37 w in S vs 646+/-69 w in UT) and Lamax (16.8+/1.8 mmol x l(-1) in S vs 12.2+/-2.5 mmol x l(-1) in UT). At the end of the test the NAmax values were similar in both groups whereas the Amax were significantly higher in S (7.6 +/- 1.4 nmol x l(-1) in S vs 3.6 +/- 3.2 nmol x l(-1) in UT). This leads to a higher Amax/NAmax ratio for sprinters compared to untrained subjects (0.7+/-0.2 in S vs 0.3+/-0.2 in UT, p < 0.05). As the disappearance of A (estimated by the Amax-A5 difference) was not lower in S (6.4+/1.5 nmol x l(-1) in S vs 1.8+/-4 nmol x l(-1) in UT), the higher Amax values in S might be explained by a greater secretion level of A. Conversely the identical NAmax values in both groups suggested that this kind of exercise induced the same sympathetic input in S and UT. Consequently the higher Amax/NAmax ratio in S argued in favor of a higher responsiveness of the adrenal medulla of sprinters to the same sympathetic input.

Adrenal Medulla↗

PubMed1998

Experimental and clinical methods in the development of anti-Alzheimer drugs.

Methodology used for the development of anti-Alzheimer's disease (AD) drugs raises specific problems which are rarely examined in the literature. While the general development scheme is similar to that required for most drugs, some specific aspects must be analyzed, highly dominated by the dual goal of pharmacology, i.e., to obtain both symptomatic and etiopathogenic drugs. During preclinical studies, aged or lesioned animals are mainly useful for symptomatic drugs, whereas transgenic models or neurodegeneration-induced techniques would probably lead to etiopathogenic drugs potentially slowing down the process of AD. The first administrations of a new compound to human beings raise the question of the activity measurement techniques. Psychometry remains the most informative procedure to detect and analyze the activity of the drugs on the different components of cognition. Electrophysiology and neuroimaging need some complementary studies before they can be proposed as surrogate criteria in phase III trials. At this stage of development, American and the recently published European guidelines are of great help while insisting on long-term (6 months) placebo controlled trials with the use of the triple efficacy criterion: an objective cognition scale, a global assessment, and the opinion of the caregiver. In the long term, pharmacoepidemiology and pharmacoeconomy will have to confirm the rationale of this recent progress in the methodology of anti-AD drug development.

Aging↗

PubMed1998

Clinical efficacy of almitrine-raubasine. An overview.

Different pharmacological properties of almitrine-raubasine show that this combination may be a good therapy for the treatment of age-related cerebral disorders and functional rehabilitation after stroke. Many clinical studies have been carried out in France and in the rest of Europe, confirming the value of this compound in such situations. Without discussing the complexity of clinical trials in both the areas of cognitive disorders and stroke, we shall present two studies demonstrating the beneficial effects of almitrine-raubasine against cognitive impairments. The first is a double-blind controlled study versus placebo with a 3-month follow-up period involving patients (aged between 60 and 85) with memory loss, lack of concentration, impaired mental altertness, and emotional instability. The second is a controlled multicenter study of 155 outpatients (age 70-85) presenting with cognitive decline (assessed by MMSE, SCAG). In both these studies, almitrine-raubasine significantly improved symptomatology and was superior to placebo, especially in the vascular cases. This confirms the validity of previous studies and justifies the indication of these compounds in the treatment of age-related cognitive disorders. Other studies also demonstrated the beneficial effect of this compound on neurosensory vascular disorders, with specific studies carried out on chorioretinal dysfunctions (visual symptomatology) and in vestibular disorders (vertigo associated with electronystagmographic modifications). The appropriate and usual dosage (2 tablets per day) and the good tolerance of the compound have been confirmed in a French multicentric study in 5,361 outpatients.

Aged↗

PubMed1997

Lisuride prevents learning and memory impairment and attenuates the increase in extracellular dopamine induced by transient global cerebral ischemia in rats.

In this experiment, we tested the efficacy of neuroprotection with lisuride, a dopamine agonist, using the 4-vessel occlusion rat model. Functional improvement was evaluated with two behavior tests exploring learning and memorization capacity in the rat, the Morris water maze and the 14-unit T-maze, 18 days after ischemia. Extracellular dopamine levels during ischemia were determined in search of a possible neuroprotection mechanism. Dopamine and its metabolites, DOPAC and HVA, as well as the serotonin metabolite, 5-HIAA, were assayed with HPLC-EC, in striatal extracellular fluid obtained by in vivo microdialysis in the awake rat. Lisuride was administered at a total dose of 10 ng by continuous intrastriatal infusion or at the dose of 0.5 mg/kg by i.p. infusion, 160 minutes before onset of ischemia for the neurochemical study and at the dose of 0.5 mg/kg via i.p. infusion, 1 hour before occlusion of the carotid arteries, for the behavior tests. Behavioral testing showed significantly better recovery in both sets of behavioral tests, with more pronounced positive results with the 14-unit T-maze, in comparison with the saline-treated animals. Microdialysis confirmed a significant attenuation of the ischemia-induced dopamine surge, whatever the mode of administration, compared with saline-treated animals. These results show that lisuride offers significant neuroprotection from the effect of experimental transient global forebrain cerebral ischemia in the rat; the mechanism would imply, at least in part, reduced levels of extracellular dopamine.

Animals↗