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At least 343 records · Page 19Linked to original sources
PubMed2000

[Akatinol memantin in Alzheimer's disease: clinico-immunological correlates].

16 patients with Alzheimer's disease were treated with akatinol memantine. The levels of production of interleukin-1 (IL-1) in lymphocyte culture were evaluated both before and after the treatment that lasted for 2-4.5 months. Before the therapy a significant (p < 0.05) increase in the production of IL-1 was observed in patients with mild and moderate dementia, with early onset of the disease and with the duration of the disease up to 9 years as compared with a control group (24 healthy individuals). After the treatment the production of IL-1 was decreased in patients with moderate dementia, with early onset, and with hereditary form of the disease. Decrease of the level of IL-1 production after the treatment corresponded to improvement of the cognitive functions of the patient. In cases of unsatisfactory treatment (without any improvement of a clinical state) IL-1 production was at higher levels (p < 0.05) as compared with the control values. It is suggested that initial high level of IL-1 production could serve as a predictor of efficiency of therapy with akatinol memantine in patients with early onset of Alzheimer's disease.

Aged↗
PubMed2000

NMDA channel blockers: memantine and amino-aklylcyclohexanes--in vivo characterization.

The previous overviews provided the basis for better therapeutic efficacy/tolerability of low to moderate affinity NMDA channel blockers. This prediction finds support in in vitro studies comparing protective and plasticity impairing effects (therapeutic vs. side-effect) of memantine and (+)MK-801. In fact it turned out that memantine had a far better therapeutic index. But can it be confirmed in the in vivo situation?

Animals↗
PubMed2003

[Memantine].

Alzheimer's disease (AD) is the most common form of dementia in Western countries. The benefits presently observed with the approved treatments are mainly symptomatic without clear evidence of neuroprotection. N-methyl-D-aspartate (NMDA) receptor antagonists have very extensive therapeutic potential in several central nervous system disorders and can be used as neuroprotective treatment in chronic neurodegenerative diseases and as symptomatic treatment in other neurologic diseases as epilepsy. Memantine, an antagonist of the glutamatergic NMDA receptor, has been recently approved for the treatment of advanced AD. Due to its action mechanism, memantine is considered a neuroprotective drug, whose utility has been demonstrated in preclinical studies, and a useful symptomatic treatment for AD and vascular dementia. We will review both aspects as well as the basic mechanisms mediating glutamatergic neurodegeneration and the implication of glutamate in cognition.

Aged↗
PubMed1992

Inhibitory effects of the antiparkinsonian drugs memantine and amantadine on N-methyl-D-aspartate-evoked acetylcholine release in the rabbit caudate nucleus in vitro.

Slices of the rabbit caudate nucleus were incubated with [3H]choline or [3H]dopamine and then superfused continuously with Mg(++)-free medium. Stimulation with N-methyl-D-aspartate (NMDA), alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA), L-glutamate and kainic acid (in that rank order of potencies) caused a concentration-dependent increase in [3H]ACh efflux, which was abolished in the presence of Mg++. This kind of release was Ca(++)-dependent and tetrodotoxin-sensitive. In contrast, NMDA was hardly effective in stimulating [3H]ACh release from hippocampal or cortical slices, as well as [3H]dopamine release from slices of rabbit caudate nucleus. Hence, the presence of cell bodies of stimulated neurons seems to be a prerequisite for the induction of release via NMDA receptors. Dizocilpine [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate] at nanomolar concentrations, as well as memantine and amantadine at low micromolar concentrations, inhibited the L-glutamate- and NMDA-evoked [3H]ACh release in a concentration-dependent, noncompetitive and use-dependent manner. Also (+/-)-2-amino-5-phosphopentanoic acid at micromolar concentrations depressed the L-glutamate- and NMDA-induced release, acting, however, in a competitive manner. It is concluded that, by antagonizing NMDA receptor-mediated ACh release, memantine and amantadine may act as functional "anticholinergics" when administered clinically to treat Parkinson's disease.

Acetylcholine↗
PubMedDate not supplied

Sigma1 receptor antagonists attenuate antidepressant-like effect induced by co-administration of 1,3 di-o-tolylguanidine (DTG) and memantine in the forced swimming test in rats.

The obtained results show that DTG, the sigma1/sigma2 receptor agonist, exerts a synergistic effect with memantine, an uncompetitive NMDA receptor antagonist, in the forced swimming test in rats, and that progesterone and BD 1047, the sigma1 receptor antagonists, counteract this effect. The results suggest that the sigma1 receptor subtype may contribute to the behavioral response induced by combined administration of DTG and memantine in Porsolt's test in rats.

Animals↗
PubMed2004

[Memantine can relieve certain symptoms in Parkinson disease. Improvement achieved in two out of three described cases with dyskinesia and cognitive failure].

Parkinson's disease is a chronic, progressive, neurodegenerative disease with a reduction of dopamine levels causing the typical symptoms tremor, hypokinesia, rigidity, and postural disturbance. After some years with Parkinson's disease patients tend to develop fluctuating symptoms and dyskinesia with involuntary movements--a state difficult to manage. Different pharmacological as well as non-pharmacological strategies are used and being tried. One of these is targeting the dysfunctioning glutamatergic neurotransmitter system through the NMDA-receptors. The NMDA-receptor antagonist amantadine has long been used as an anti-Parkinson drug but also as an anti-dyskinetic drug. Recently, another NMDA-receptor antagonist, memantine, was approved for moderate to severe Alzheimer's dementia in Sweden. We describe the use of memantine on three cognitively impaired, dyskinetic Parkinsonian patients where two seemed to benefit from this medication regarding their dyskinesia.

Aged↗
PubMed2004

[Role of magnesium ions on the regulation of NMDA receptor--a pharmacopathology of memantine].

Magnesium ion blocks the ion channel of the NMDA receptor at a stable condition. The ion channel competes with the binding site of the noncompetitive antagonists phencyclidine (PCP) and MK-801, which prevent a brain impairment due to the ischemia and so on. The binding ability of these antagonists is strong, an exchange with the magnesium ion is not easy, then the side effect of the schizophrenia-like behavior is caused. Recently, memantine can be used as a therapeutic drug of the moderate-to-severe Alzheimer's disease. Memantine is the noncompetitive antagonist, too, then those development details and a difference from MK-801 were explained.

Alzheimer Disease↗
PubMedDate not supplied

[Advanced dementia in Alzheimer's disease and memantine].

INTRODUCTION: Alzheimer's disease (AD) causes dementia with a progressive course. Until now, research has been aimed mainly at studying its early, pre-dementia and mild or mild to moderate dementia phases in an attempt to find treatments with which to cure it or at least halt its progression. It is true that the latest cognitive therapies are effective up to a point, but the fact is that many patients reach the state of advanced AD, which gives rise to a number of cognitive and behavioural disorders that entail all kinds of problems on a personal, familial and community health level. AIMS: This study reviews the progress of AD, the length of its stages, the speed at which the disease courses and patients' survival. Advanced AD is defined, its clinical features and the functional disability it causes are described, and we analyse the tests and scales that must be used to measure how the process is progressing and the effectiveness of the distinct forms of treatment used in the later phase of AD, which are different to those employed in the early stages. All this allows us to analyse the results of clinical trials carried out with memantine, an NMDA (N-methyl D-aspartate) receptor antagonist. We review its pharmacological characteristics and its use in everyday practice. Lastly, we refer to the classical symptomatic treatments that are usually employed to control the frequent and intense behavioural disorders produced in the advanced phase of AD. CONCLUSIONS: The later stage of AD requires our attention because many patients reach and remain for a long time in this phase, which leads to considerable personal and social disorders. Several scales and tests have been adapted to these later phases of AD, enabling the clinician to evaluate the patient, monitor the progress of the disease and determine the effectiveness of different treatments. Memantine, the most recent drug approved for use with this disease, has proved to be effective in the treatment of patients with advanced AD. This pharmaceutical has been added to the list of well-known classical medicines, such as neuroleptic drugs, antidepressants, anxiolytic agents and others, which can be used to diminish the behavioural disorders in these patients and improve their quality of life, as well as that of their caregivers.

Alzheimer Disease↗
PubMed2006

Clinical experience with risperidone and memantine in the treatment of Huntington's disease.

We described a 32-year-old woman with Huntington's disease (HD) who presented with severe chorea, psychosis and cognitive abnormalities. We started risperidone at 2 mg p.o./d and increased to 4 mg p.o./d after six weeks. Psychotic and motor symptoms were markedly improved. Since there was no change in cognitive functions, we added memantine at 5 mg p.o./d and gradually increased the dose to 20 mg p.o/d after five weeks. We continued risperidone and memantine for nearly six months. The patient did not show any progression of cognitive symptoms or motor abnormalities. We did not observe any psychotic symptoms.

Adult↗
PubMedDate not supplied

Methyl parathion acute toxicity: prophylaxis and therapy with memantine and atropine.

Male rats administered with a single i.p. dose of 5 mg/kg methyl parathion, showed the toxic signs of hypercholinergic (anticholinesterase) activity with maximal severity, including muscle fasciculations and convulsions within 15 to 30 min, persisting for about 2 hr. The time course of acetylcholinesterase activity in discrete brain regions (cortex, stem, striatum and hippocampus), heart and hemidiaphragm, indicated its maximal depression during 30 to 60 min after administration of methyl parathion. At this time, a marked reduction in carboxylesterase activity was also evident both in neuronal and nonneuronal tissues, suggesting a tremendous binding to nonacetylcholinesterase serine sites. Pretreatment with memantine hydrochloride (18 mg/kg, i.p.) 30 min, and atropine sulfate (16 mg/kg, i.p.) 15 min before methyl parathion administration, completely prevented the expected toxic signs and significantly (P less than 0.01) attenuated the induced inhibition of acetylcholinesterase. When given therapeutically, this combined treatment completely reversed the clinical evidence of methyl parathion toxicity within 10 to 15 min and markedly reduced the acetylcholinesterase inactivation. These results suggest that memantine may counteract the acute methyl parathion toxicity by (a) protection of acetylcholinesterase from inhibition, (b) rapid reactivation of inhibited acetylcholinesterase and (c) rapid bioelimination of methyl parathion, in addition to cholinolytic effects of atropine sulfate.

Acetylcholinesterase↗
PubMedDate not supplied

In vitro electrophysiological evidence predicting anticonvulsant efficacy of memantine and flunarizine.

Electrophysiological assays on mammalian central neurons in monolayer dissociated cell culture allow classification of clinically used anticonvulsant drugs on a mechanistic basis and predict their clinical spectrum of anticonvulsant efficacy consistently in comparison with data from animal models. Clinical anticonvulsant efficacy of memantine and flunarizine against tonic-donic and partial seizures is predicted on the basis of ability to limit sustained high efficacy frequency repetitive firing of sodium-dependent action potentials and to suppress depolarizing burst firing of neocortical, hippocampal and spinal cord neurons in cell culture. Effects on voltage-sensitive sodium channels, and possibly potassium channels, may explain, at least in part, the mechanism of anticonvulsant efficacy of memantine and flunarizine.

Amantadine↗
PubMed1982

[Effect of memantine on central neurotransmitter systems. Review of the results].

In the present review the effects of 1,3-dimethyl-5-amino-adamantane (DMAA, D-145, Memantine, Memantine) on various neurotransmitter systems were presented. The most marked effect of DMAA seems to be the stimulation of dopaminergic neurons as reflected by the respective behavioural changes and biochemical effects. The stimulatory action on noradrenaline and serotonin neurons (at least partially indirectly through the activation of dopamine system) as well as on GABA neurons is apparent. No direct effects on Dopamine, alpha 1, alpha 2, Serotonin, GABA, benzodiazepine and opiate receptors were found. DMAA can be assigned to a new class of compounds which act mainly as dopaminomimetics, but its mode of action is apparently different from those of amphetamine or apomorphine. It differs quantitatively and qualitatively from amantadine, another derivative of adamantane.

Acetylcholine↗
PubMed1982

[Effect of memantine on membrane properties and postsynaptic potentials in neurons of Aplysia californica].

The effect of 1,3-dimethyl-5-aminoadamantane (DMAA, D-145, memantine, Memantine) in the concentration range of 10(-6) to 10(-3) mol/l was investigated on membrane properties and synaptic transmission by the current or voltage clamp method on neurons in the visceral ganglion of Aplysia california. In the lower range (concentrations 10(-6) to 10(-5) mol/l) the substance increases the speed of voltage changes during the course of the action potential, increases spontaneous synaptic activity, and induces a slight membrane depolarization. With increasing concentration the effects reverse in that slope of action potential is slowed and synaptic transmission delayed or blocked. At the RC-R15 synapse, isolated from its interneuron, 10(-5) mol/l DMAA evokes spontaneously and regularly firing EPSPs; 10(-3) mol/l blocks both, spontaneous activity, and its responsiveness to electrical stimulation.

Action Potentials↗
PubMed1998

Memantine attenuates responses of spinothalamic tract cells to cutaneous stimulation in neuropathic monkeys.

Several lines of evidence indicate that N-methyl-D-aspartate (NMDA) receptors play an important role in nociception in general and in pathological pain in particular. It has been previously demonstrated in behavioral studies that NMDA receptor antagonists attenuate pathological pain in humans and nociceptive behaviors in animals. In the present study, we investigated the effect of the NMDA receptor antagonist memantine (MEM) on the responses of spinothalamic tract (STT) cells in normal and neuropathic monkeys. Memantine was delivered into the spinal cord through a microdialysis fiber acutely implanted into the dorsal horn. Responses of STT cells to peripheral stimulation within their receptive fields were recorded before and after MEM infusion. In normal animals (n = 7), 10 mm MEM did not affect STT cell (n = 7) baseline activity or responses to mechanical stimuli (brush, press or pinch). In neuropathic animals (n = 6), 1.0, 3.0, 10.0 and 100 mm MEM did not affect baseline activity of STT cells (n = 7); however, in a dose-dependent fashion, it significantly reduced responses of these cells to all cutaneous stimuli. The data suggest that MEM can have a direct effect on STT cells, blocking NMDA receptors known to be present on this cell population and, furthermore, may be a therapeutic agent for chronic pain.

Journal Article↗
PubMed2004

Review of donepezil, rivastigmine, galantamine and memantine for the treatment of dementia in Alzheimer's disease in adults with Down syndrome: implications for the intellectual disability population.

The management of dementia in Alzheimer's disease has dramatically changed since the development of anti-dementia drugs. However, there is limited information available regarding the bio-medical aspects of the differing drugs; particularly relating to adults with intellectual disability. Indeed the information available for the intellectual disabled population is limited to adults with Down syndrome. This review highlights the important pharmacological and clinical aspects of donepezil, rivastigmine, galantamine and memantine and supports the view that such drugs play an important part in the management of dementia in adults with intellectual disability. Future clinical and research issues are discussed.

Alzheimer Disease↗
PubMed2003

Treating the full spectrum of dementia with memantine.

An increasing number of elderly people result in increased social and economical impact of dementia, particularly its most common form Alzheimer's disease (AD). Dementia itself consists of a wide spectrum of disease, ranging from the mild cognitive impairment that progresses through several clinical milestones to advanced dementia. Drugs available at the moment on the market are approved for the treatment of mild to moderate dementia and their symptomatic effect is based on cholinergic substitution. However, the largest amount of costs utilised for dementia is institutional care for severely affected patients. At this stage of the disease both vascular and degenerative mechanisms contribute to the clinical expression of the disease. Recent clinical trials with the antiglutamatergic drug memantine have shown that cognitive benefit could be observed in patients with vascular dementia and reduced care dependence in those with moderately severe to severe form of the disease. The later findings are results from the M-BEST study, which is briefly rewieved here with some of the epidemiological, socioeconomical and clinical implications of such therapy.

Aged↗
PubMed2000

Role of high-energy phosphates and their metabolites in protection of carbofuran-induced biochemical changes in diaphragm muscle by memantine.

A combined antidotal treatment with memantine HCI (MEM, 18 mg/kg, s.c.) and atropine sulfate (ATS, 16 mg/kg, s.c.) provided complete protection against acute carbofuran toxicity (1.5 mg/kg, s.c.) in rats by multiple mechanisms. Carbofuran, in addition to inhibiting serine-containing esterases, also perturbed the activities of mitochondrial/cytoplasmic biomarker enzymes (creatine kinase, CK; and lactic dehydrogenase, LDH) in diaphragm muscle. The observed changes in the activity of biomarker enzymes were reflected in serum as a result of their leakage from the diaphragm due to a depletion of high-energy phosphates, such as adenosine triphosphate (ATP, 27%) and phosphocreatine (PCr, 33%) and their metabolites (ADP, 36%; AMP, 35%; and Cr, 38%). Combined treatment with MEM and ATS provided protection and reversal of the induced changes in biomarkers by preventing depletion of high-energy phosphates and thus maintaining normal cell membrane characteristics, including permeability and integrity. These results, along with those reported previously, indicate that MEM antagonizes carbofuran toxicity by multiple mechanisms.

Acetylcholinesterase↗