Глутаматергические механизмы ОКР

Glutamatergic Dysfunction in Obsessive-Compulsive Disorder and the Potential Clinical Utility of Glutamate-Modulating Agents

Мемантин

"This study elegantly demonstrates how memantine is able to protect neurons without causing harmful side effects," said Giles E. Hardingham, BSc, PhD, professor of molecular neurobiology, University of Edinburgh in the United Kingdom, who was not involved in the study.

"Memantine only blocks NMDA receptors when they are engaged in harmful activities away from the synapse; it does not interfere with the normal functioning of the NMDA receptor at the synapse," Dr. Hardingham explained.

Memantine's Unique Mechanism of Action Uncovered

Сосудистая деменция: фармакотерапия

Vascular dementia is a common condition for which there are no effective approved pharmacological treatments available. Absence of effective treatments creates a difficult situation for those suffering from the disease, their caregivers, and healthcare providers. This review will address our current understanding of the mechanisms of nerve cell damage due to ischemia and summarize available clinical trial data on several commonly used compounds including memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDP-choline, folic acid, as well as such nonpharmacological approaches as validation therapy.

From the studies reviewed here, one may draw several conclusions. First, there are relatively few studies on vascular dementia treatment and no compound has been approved by any regulatory body for treatment of vascular dementia. Second, it appears that there are several compounds with different mechanisms of action that show mild efficacy in improving cognition and even ADLs in patients with vascular dementia. Third, there is one compound (memantine) that has been suggested to act within the confines of the current excitotoxic cell death model, although direct evidence confirming this hypothesis is still lacking. Overall, one could easily conclude that a number of different mechanisms may be at play in ethiopathogenesis of vascular dementia. Vascular conditions aside, nerve cell resistance to injury and our efforts to manipulate it still remains a conundrum, which will require new technologies to solve.

Vascular dementia: Pharmacological treatment approaches and perspectives

Резистентные к лечению депрессии

Antidepressants can be grouped into 6 major categories: tricyclic antidepressants (TCAs), SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), serotonin neurotransmitter (5-HT2)-receptor antagonists (eg, nefazodone, trazodone), and novel agents (eg, mirtazapine, bupropion). If a patient fails to respond to one antidepressant class, it makes sense (at least conceptually) to switch to another, although most guidelines acknowledge that 2 failed trials of SSRIs may be justifiable before switching classes.
For example, in a study by Thase and colleagues,10 58 patients failed a trial of fluoxetine; however, there was a 76% response rate to citalopram among completers. Although this study was not blinded, it is interesting that citalopram (which is believed to be the most selective of the SSRIs) was effective when another SSRI was not.
Antidepressants that are associated with discontinuation symptoms (eg, paroxetine, venlafaxine, duloxetine) may produce discontinuation syndromes when stopped that can be erroneously attributed to adverse effects of the new drug, particularly if the new drug does not possess a significant degree of serotonin reuptake inhibition.
In a study by Zarate and colleagues,21 the onset of the antidepressant effect of ketamine occurred within 2 hours. Unfortunately, the drug must be given by intravenous infusion, but because the effect persisted for 7 days, ketamine treatment may be useful if given as a series.
Another NMDA-receptor antagonist now available in the United States is memantine (FDA-approved for Alzheimer disease). Memantine was shown to be effective in an open-label study in major depression. In a double-blind, randomized trial it showed comparable effects to escitalopram in patients with major depression and alcohol dependence.
Randomized controlled trials have supported the superior efficacy of a TCA/SSRI combination, as well as a mirtazapine/SSRI combination; open studies have done the same for TCA/MAOI and SSRI/bupropion combinations.
As with lithium, a recent review concluded that the trial data that support the efficacy of T3 augmentation are of better quality with TCAs than with SSRIs

Treatment-Resistant Depression