Effect Of Oxiracetam Research Articles

Observation on clinical effect of oxiracetam combined with nimodipine in the treatment of vascular dementia

Objective To observe the clinical effects of oxiracetam combined with nimodipine in the treatment of vascular dementia.Methods 80 patients with vascular dementia in our hospital from May 2011 to March 2013 were randomly divided into observation group and control group,40 cases in each group.Observation group was given oxiracetam combined with nimodipine based on the general conventional method,and control group was given only general conventional method.Then the curative effects of two groups were analyzed and compared.Results After treatment,the clinical effect,MMSE grade,and ADL grade in the observation group were significantly better than those in the control group.Conclusion The curative effect of the oxiracetam combined with nimodipine in the treatment of vascular dementia is exact,which has collaborative strengthening effect.It is worthy to be popularized in clinic. Key words: Oxiracetam; Nimodipine; Vascular dementia

Cognition Enhancing Profile of CR 2249, a New NMDA‐Glycine Site Modulator

Memory processes have been widely studied in recent decades. Unfortunately, although several intriguing hypotheses about the possibility of modulating cognition have been developed, no conclusive result has been obtained (69). Two different neurotransmission models are of major interest in understanding how the brain can acquire and store a single cognitive event (3,23). The main neuronal agents involved in transferring this kind of information seem to be acetylcholine and glutamic acid. These two neurotransmitters are present in all the cerebral areas involved in the memory processes and both are responsible for the stimulation currents linked to the propagation of neuronal signals (1,4). The cholinergic hypothesis of memory ( 3 ) is based on the observation that a marked degeneration of the cholinergic neuronal pathway is often associated with the development of cognitive disorders ( 12). Moreover, it has been reported that one distinctive feature of Alzheimer’s disease (AD) consists of a progressive loss of either cholinergic or adrenergic neurons’ ability to transmit stimuli received from the limbic areas to the cerebral cortex (10,12,21,75). To help preserve high levels of acetylcholine in the synaptic cleft, several antiacetylcholinesterase agents have been synthesized and tested on both biochemical and behavioral models of learning (32,46). Tacrine is certainly the most studied among these agents ( 13). Clinical trials with tacrine revealed some interesting pro-mnemic properties of this compound (42,68), but tacrine exhibits major hepatotoxicity that strongly restricts its use ( 13,73). Donepezil (E2020) is another interesting compound of this family. Two recently published clinical studies (25,63) demonstrate both the efficacy of donepezil in patients with mild-to-moderate Alzheimer’s disease and its relative liver safety. Other potent acetylcholinesterase inhibitors, such as metrifonate and SDZ ENA 7 13, are currently under clinical evaluation (28,62,65). The glutamatergic hypothesis of memory is based on a particular characteristic of the glutamatergic neuronal pathway: long-term potentiation (LTP). LTP was first defined by Bliss and Collingridge (8) as a synaptic memory model expressed as a persistent increase in the size of the synaptic component of the evoked response. The

Oxiracetam and aniracetam increase acetylcholine release from the rat hippocampus in vivo

AbstractThe effect of two nootropic drugs, oxiracetam and aniracetam, on cholinergic neurotransmission in vivo was investigated in the rat by means of the transversal microdialysis techique. The basal release of acetylcholine (ACh) from the hippocampus and parietal cortex was 2.93 ± 0.17 and 3.10 ± 0.18 pmol/min (mean ± s.e.m.), respectively, and remained stable for at least 3 h, while the initial efflux of choline was 51.9 ± 2.6 and 42.8 ± 6.4 pmol/20 min (mean ± s.e.m.), respectively, and decreased by about 50% during the first 60 min of collection. Oxiracetam, tested at doses of 50, 100, and 300 mg/kg ip, elicted a 63% increase in ACh release from the hippocampus at the dose of 100 mg/kg only. This effect of oxiracetam was inhibited by perfusion with tetrodotoxin (TTX), 5 × 10−7 M. In oxiracetam‐treated rats the decrease in choline efflux was less pronounced than in controls (‐23% of the initial value) at the dose of 100 mg/kg. Aniracetam (100 mg/kg, orally) elicited a sustained increase of ACh release from the hippocampus (+ 58%, 120 min after the administration), without affecting choline efflux. Doses of 50 and 300 mg/kg, orally, of aniracetam were ineffective. Oxiracetam and aniracetam (50 and 100 mg/kg) neither modified the output of ACh or choline from the parietal cortex nor induced gross behavioral changes. These results indicate that oxiracetam and aniracetam could act on cognitive processes by stimulating the hippocampal cholinergic pathways. © Wiley‐Liss, Inc.

Effect of oxiracetam on scopolamine-induced amnesia in the rat in a spatial learning task

The effects of the nootropic agent 4-hydroxy-2-oxopyrrolidinoacetamide (oxiracetam) on memory and performance impairments induced by scopolamine were evaluated in the Morris water maze task. No effect was seen on the performance of rats when treated with oxiracetam (30 mg/kg, IP) alone. Task performance of scopolamine (0.2 mg/kg, SC)-treated rats was impaired as compared to that of control animals. The behavioral deficits expressed in the task by scopolamine treatment were attenuated by the same dose of oxiracetam.

A decrease in brain catecholamines prevents oxiracetam antagonism of the effects of scopolamine on memory and brain acetylcholine

The effect of oxiracetam on passive avoidance conditioned response and acetylcholine (ACh) levels in rats with selective lesions of the central monoaminergic pathways was investigated. The lesions were followed by a marked decrease in cortical serotonin (−88%), noradrenaline (−54%) and striatal dopamine (−57%) levels, while neither the performance of a passive avoidance conditioned response nor brain ACh levels were affected. Scopolamine (hyoscine) administration (0.63 mg/kg, s.c.) to lesioned rats exerted the expected amnesic effect, associated with a decrease in hippocampal, cortical and striatal ACh levels. In the rats with degeneration of dopaminergic and noradrenergic but not serotoninergic pathways, oxiracetam (50 and 100 mg/kg, s.c.) was unable to prevent both amnesia and the decrease in brain ACh levels caused by scopolamine. The effect of oxiracetam was prevented by haloperidol (0.2 mg/kg, s.c.). Our findings support the hypothesis that an interaction between monoaminergic and cholinergic neurotransmitter systems may be involved in the actions of nootropic drugs on cognitive functions.

P-248 - Effect of oxiracetam (CT-848) on the reduction of local cerebral glucose utilization after focal cerebral ischemia in rats.

P-248 - Effect of oxiracetam (CT-848) on the reduction of local cerebral glucose utilization after focal cerebral ischemia in rats.

Effect of oxiracetam and piracetam on cerebral cortical unit activity

Effect of oxiracetam and piracetam on cerebral cortical unit activity

Double-Blind Placebo-Controlled, Neuropsychological and Neurophysiological Investigations with Oxiracetam (CGP 21690E) in Memory-Impaired Patients with Epilepsy

A double-blind placebo-controlled between-patient study was carried out to assess the effects of oxiracetam (CGP 21690E) on memory function in patients with epilepsy. During a 12-week period, either oxiracetam (800 mg t.i.d.) or placebo was given to 30 patients. Twenty-four of the patients had a partial epilepsy. Most patients were on monotherapy carbamazepine. Effect of oxiracetam on memory and related cognitive functions were assessed, using a computerized neuropsychological testing method, while concomitant electrophysiological changes were investigated with routine EEG registration, power spectrum analysis and auditory evoked event-related potentials (P300). Subjective evaluation of well-being was quantified with a mood rating scale. The results did not show any meaningful changes in memory function. This finding is in line with the subjective patient reports and the P300 measures.

Effect of oxiracetam on cerebral cholinergic imbalance secondary to an nmda-receptor blockade

Nearly three decades have now passed since the discovery of the piracetam-like nootropics, compounds which exhibit cognition-enhancing properties, but for which no commonly accepted mechanism of action has been established. This review covers clinical, pharmacokinetic, biochemical and behavioural results presented in the literature from 1965 through 1992 (407 references) of piracetam, oxiracetam, pramiracetam, etiracetam, nefiracetam, aniracetam and rolziracetam and their structural analogues. The piracetam-like nootropics are capable of achieving reversal of amnesia induced by e.g., scopolamine, electrocon-vulsive shock and hypoxia. Protection against barbiturate intoxication is observed and some benefit in clinical studies with patients suffering from mild to moderate degrees of dementia has been demonstrated. No affinity for the α1-, α2-, β-, muscarinic, 5-hydroxytryptamine-, dopamine, adenosine-A1, μ-opiate, γ-aminobutyric acid (GABA) (except for nefiracetam (GABAA)), benzodiazepine and glutamate receptors has been found. The racetams possess a very low toxicity and lack serious side effects. Increased turnover of different neurotransmitters has been observed as well as other biochemical findings e.g., inhibition of enzymes such as prolylendopeptidase. So far, no generally accepted mechanism of action has, however, emerged. We believe that the effect of the racetams is due to a potentiation of already present neurotransmission and that much evidence points in the direction of a modulated ion flux by e.g., potentiated calcium influx through non-l-type voltage-dependent calcium channels, potentiated sodium influx through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor gated channels or voltage-dependent channels or decreases in potassium efflux. Effects on carrier mediated ion transport are also possible.

Effect of Oxiracetam and Piracetam on Central Cholinergic Mechanisms and Active-Avoidance Acquisition

Oxiracetam at 100 and 300 mg/kg i.p. dose levels increased acetylcholine (ACh) utilization in the rat cerebral cortex and hippocampus. ACh utilization was assessed by measuring, with a gas chromatographic method, the decrease in ACh level after inhibiting its synthesis by 15 micrograms intracerebroventricularly (i.c.v.) injection of hemicholinium (HC-3). ACh steady state levels were not affected. Piracetam (300 mg/kg i.p.) also increased ACh utilization in the hippocampus. Repeated daily administration of oxiracetam 100 mg/kg i.p. caused a 31% increase in high-affinity choline uptake (HACU) in the hippocampus. A single administration of 300 mg/kg i.p. of oxiracetam and piracetam also increased HACU rate in the hippocampus. However, the effect of piracetam was over within 3 h, while 3 h after its administration oxiracetam still caused a 40% increase in HACU rate. Oxiracetam (100 mg/kg i.p.) significantly antagonized the impairment in the acquisition of an active-avoidance conditioned response (pole climbing) associated with the inhibition of ACh synthesis by HC-3. These results indicate that oxiracetam enhances the activity of the septohippocampal cholinergic pathways, and to a lesser extent, of the cortical cholinergic network.

Effect of Oxiracetam and Piracetam on Central Cholinergic Mechanisms and Active-Avoidance Acquisition

Clinical Neuropharmacology is a peer-reviewed journal devoted to the pharmacology of the nervous system in its broadest sense. Coverage ranges from such basic aspects as mechanisms of action, structure-activity relationships, and drug metabolism and pharmacokinetics, to practical clinical problems such as drug interactions, drug toxicity, and therapy for specific syndromes and symptoms. The journal publishes original articles and brief reports, invited and submitted reviews, and letters to the editor. A regular feature is the Patient Management Series: in-depth case presentations with clinical questions and answers.