Search results for "Memantine"

Role of N-methyl-D-aspartate receptors in the long-term effects of repeated social defeat stress on the rewarding and psychomotor properties of cocai…

2019

Abstract Exposure to social stress increases the vulnerability of experimental animals to the rewarding effects of cocaine and it has been suggested that the glutamatergic system could be involved in these effects of stress. The aim of this work is to determine the role of N-methyl- d -aspartate (NMDA) glutamate receptors in the influence of social stress on the conditioned place preference and locomotor sensitization induced by cocaine. Mice treated with saline or NMDA antagonist memantine (5 or 10 mg/kg) underwent repeated social defeat or were kept in the exploration control condition. After three weeks, all groups (SAL + RSD, M5 + RSD, M10 + RSD, SAL + EXP, M5 + EXP and M10 + EXP) were …

Synthesis and pharmacological evaluation of several ring-contracted amantadine analogs

2008

Graphical abstract Several bisnoradamantylamines and noradamantylamines have been synthesized and their antiviral, trypanocidal, NMDA receptor antagonist, and dopamine reuptake inhibitory activities have been studied.

Controlled Iontophoretic Delivery in Vitro and in Vivo of ARN14140—A Multitarget Compound for Alzheimer’s Disease

2019

ARN14140 is a galantamine-memantine conjugate that acts upon both cholinergic and glutamatergic pathways for better management of Alzheimer's disease. Poor oral bioavailability and pharmacokinetics meant that earlier preclinical in vivo studies employed intracerebroventricular injection to administer ARN14140 directly to the brain. The aim of the present study was to evaluate the feasibility of using constant current transdermal iontophoresis for the noninvasive systemic delivery of ARN14140 and to quantify the amounts present in the blood and the brain. Preliminary experiments in vitro were performed using porcine skin and validated with human skin. Cumulative ARN14140 permeation across th…

Neuroactive compounds produced by bacteria from the marine sponge Halichondria panicea: activation of the neuronal NMDA receptor

1998

Abstract Previous studies revealed that the marine sponge Halichondria panicea habors symbiotic- and commensalic bacteria ( Althoff et al., 1998 . Marine Biol. 130, 529–536). In the present study the hypothesis was tested whether some of those bacteria synthesize neuroactive compounds. For the first time the effect of bacterial bioactive compounds on the neuronal ionotropic glutamate receptors [iGluR], subtype N -methyl- d -aspartate (NMDA) receptor, was checked. In cortical neurons from rats as cell system the supernatant of two bacterial cultures isolated from H. panicea proved to agonize the NMDA receptor. The response of the NMDA receptor to the bioactive compounds was determined by mea…

Modulation of Neurological Deficits and Expression of Glutamate Receptors during Experimental Autoimmune Encephalomyelitis after Treatment with Selec…

2013

The aim of our investigation was to characterize the role of group I mGluRs and NMDA receptors in pathomechanisms of experimental autoimmune encephalomyelitis (EAE), the rodent model of MS. We tested the effects of LY 367385 (S-2-methyl-4-carboxyphenylglycine, a competitive antagonist of mGluR1), MPEP (2-methyl-6-(phenylethynyl)-pyridine, an antagonist of mGluR5), and the uncompetitive NMDA receptor antagonists amantadine and memantine on modulation of neurological deficits observed in rats with EAE. The neurological symptoms of EAE started at 10-11 days post-injection (d.p.i.) and peaked after 12-13 d.p.i. The protein levels of mGluRs and NMDA did not increase in early phases of EAE (4 d.p…

Novel approaches in diagnosis and therapy of Creutzfeldt-Jakob disease.

2000

The scrapie prion protein, PrP(Sc), as well as its peptide fragment, PrP106-126, are toxic on neuronal cells, resulting in cell death by an apoptotic, rather than necrotic mechanism. The apoptotic process of neuronal cells induced by prion protein supports diagnosis and offers potential targets for therapeutic intervention of the prion diseases. Among the cerebrospinal fluid (CSF) proteins, which may serve as markers of neuronal cell death associated with prion diseases, the 14-3-3 protein(s) turned out to be the most promising one. A new sensitive assay allows the detection of even small changes in the normally low levels of these proteins. In vitro, the toxic effects displayed by PrP(Sc) …

Memantine presents different effects from MK-801 in motivational and physical signs of morphine withdrawal

2003

Adaptive changes in neural systems due to chronic opiate exposure are related to the neural plasticity phenomenon, NMDA receptors being implicated in these processes, e.g. tolerance, dependence or withdrawal. In this work, we investigated the effect of two non-competitive NMDA antagonists, memantine and MK-801, in motivational (Conditioned Place Aversion paradigm, CPA) and physical aspects of morphine withdrawal. After the induction of morphine dependence, animals in which the CPA was studied, received memantine (5 and 10 mg/kg) or MK-801 (0.3-0.006 mg/kg) either during the acquisition (conditioning) or expression (test) phase of this procedure. Both drugs were capable of inhibiting conditi…

2021

Four drugs are currently approved for the treatment of Alzheimer’s disease (AD) by the FDA. Three of these drugs—donepezil, rivastigmine, and galantamine—belong to the class of acetylcholine esterase inhibitors. Memantine, a NMDA receptor antagonist, represents the fourth and a combination of donepezil and memantine the fifth treatment option. Recently, the gut and its habitants, its microbiome, came into focus of AD research and added another important factor to therapeutic considerations. While the first data provide evidence that AD patients might carry an altered microbiome, the influence of administered drugs on gut properties and commensals have been largely ignored so far. However, t…

The NMDA receptor complex: a promising target for novel antiepileptic strategies.

2001

Antiepileptic drugs (AEDs) cover a broad spectrum of pathological conditions ranging from seizures following congenital or acquired brain disorders to behavioural and psychiatric disorders and recently neuropathic pain. The need for novel antiepileptics raises from the expanding field of indications as well as from the fact, that special seizure types are refractory to common AEDs. In addition, many of the conventional antiepileptic drugs exhibit an unfavourable side-effect profile. Since there is growing evidence, that NMDA receptor activation might play a crucial role in epilepsy, NMDA receptor antagonists have become compounds of interest in preventing and treating seizures. This review …

Von der symptomatischen zur kausalen Therapie?

2009

Until today the pharmacological therapy of Alzheimer’s disease (AD) is still limited to symptomatic temporary improvement or stabilization of cognitive performance and activities of daily living, and the reduction of neuropsychiatric symptoms of the disease. Available symptomatic treatment options are the acetylcholinesterase inhibitors (ACh-I) donepezil, galantamine, rivastigmine, and the partial N-Methyl-D-Aspartat-(NMDA)-antagonist memantine. Further substances with symptomatic targets, especially selective acetylcholine and histamine receptors, are currently under development. Numerous of disease-modifying substances mainly targeting components of the amyloidogenic pathway of AD are pre…