The role of NMDA receptor antagonists, amantadine and memantine, in schizophrenia treatment: a systematic review

Junho, Bruno Terra; Oliveira, Victor Fernandes de

doi:10.1590/0101-60830000000218

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…The efficacy of Memantine in schizophrenia has been demonstrated in clinical trials in which Memantine has been associated with antipsychotic treatment in patients with chronic disease [ 124 ], cognitive deficits [ 125 ], predominance of negative symptoms [ 126 , 127 ], or in patients with positive and negative symptoms [ 128 ]. Patient aggression is associated with glutamate hyperactivity, and the use of Memantine in combination therapies has been based on the glutamatergic hypothesis of schizophrenia and the major role played by NMDA receptors [ 129 ].…”

Section: ⧉ Effectiveness Of Memantine and Amantadine In Smi Treatmentmentioning

confidence: 99%

SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine

Marinescu¹,

Marinescu²,

Mogoantă³

et al. 2021

Rom J Morphol Embryol

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This is an open-access article distributed under the terms of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License, which permits unrestricted use, adaptation, distribution and reproduction in any medium, non-commercially, provided the new creations are licensed under identical terms as the original work and the original work is properly cited. REVIEW SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and AmantadineILEANA MARINESCU 1) , DRAGOŞ MARINESCU 2) , LAURENŢIU MOGOANTĂ 3) , ION CRISTIAN EFREM 4) , PUIU OLIVIAN STOVICEK 5)

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Section: ⧉ Effectiveness Of Memantine and Amantadine In Smi Treatmentmentioning

confidence: 99%

SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine

Marinescu¹,

Marinescu²,

Mogoantă³

et al. 2021

Rom J Morphol Embryol

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“…Amantadine is the only medication approved by Food and Drug Administration (FDA) for LID therapy ( Sharma et al ., 2018 ). It normalizes excitatory signals by maintaining the closed status of glutamate N-methyl-D-aspartate (NMDA) receptor channels and reducing calcium influx into the postsynaptic neurons ( Blanpied et al ., 2005 ; Inzelberg et al ., 2006 ; Junho and de Oliveira, 2019 ). However, its narrow therapeutic window along with severe side effects, including constipation, vomiting and decreased appetite, makes it difficult for the patients to take the medication ( Pandey and Srivanitchapoom, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

5-Hydroxytryptophan Reduces Levodopa-Induced Dyskinesia via Regulating AKT/mTOR/S6K and CREB/ΔFosB Signals in a Mouse Model of Parkinson’s Disease

Choi

Huh

Lee

et al. 2023

Biomol Ther (Seoul)

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Long-term administration of levodopa (L-DOPA) to patients with Parkinson's disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor manifestations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

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“…Мемантин-неконкурентный антагонист NMDA, применяемый при «умеренной» и тяжелой степени болезни Альцгеймера, исследовался как средство аугментации различных антипсихотиков в отношении негативных симптомов, и когнитивных нарушений при расстройствах шизофренического спектра. По мнению некоторых авторов, данный препарат не эффективен при подобных ситуациях, и порой вызывает больше побочных эффектов, чем плацебо[115]. Другие авторы не разделяют подобного пессимизма, рекомендуя использовать Мемантин при шизоаффективных расстройствах, как средство аугментации, и в качестве противорезистентной терапии[116; 117].Препараты для лечения зависимости от психоактивных веществЗлоупотребление различными психоактивными веществами пациентами с расстройствами шизофренического спектра, является огромной, и с каждым годом все более актуальной клинической проблемой в процессе терапевтического вмешательства.…”

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“Golden Shot” in the Treatment and Diagnosis of Schizophrenia: Psychiatrists or Neuroscientists?

Dubatova

Antsyborov

Kheigetian

et al. 2021

ISci

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The available published data indicate that antagonism towards D2 receptors of dopamine is a «necessary condition» in the process of effective treatment of schizophrenia, but at the same time, this antagonism is insufficient to achieve a state of complete remission. These data serve as a powerful stimulus for the process of searching new treatments and synthesizing new drugs. The current status of the theory of neural networks demonstrates to the professional community that in order to effectively change the functioning of basic biological systems, a number of subtle changes in the central nervous system are required, which are possible with the use of certain substances. The influence of modulation of glutamate on these processes is currently a very «popular» direction both in neurobiology and in clinical psychiatry. At the same time, the role of the latter in the pathogenesis of a number of mental disorders remains unproven. In parallel with this direction, the mechanisms of serotonergic and cholinergic effects on the main components of the pathogenesis of mental disorders are being studied and used in the development of new antipsychotic drugs. Most antipsychotic drugs which belong to «new wave» exhibit an affinity for different types of receptors, which mediate the effect on several therapeutic targets. In practice, a large number of patients take certain drugs not only as monotherapy, but often combine them with other drugs. At the same time, the effectiveness of such therapeutical regimens is low. Therefore, in most modern protocols, monotherapy is still recommended. In recent years, there has been a growing body of research on pharmacotherapy augmentation strategies. The results of these studies demonstrate that augmentation preparations belonging to different pharmacological classes can be generally effective, not only in certain diseases, but also in certain types of patients. In attempts to create a model of «rational polypharmacy», it is very important to accurately define and target the therapy to «problematic symptoms», and it is also necessary to develop an optimal withdrawal strategy from the active therapy regimen. To date, the only existing «lifeline» is Clozapine, which, despite its many disadvantages, remains an effective therapeutic agent for resistant forms of schizophrenic spectrum disorders. New methods of drug synthesis, including «individual drug affinity» analysis and strategies based on the study of gene polymorphism, look promising in the context of antipsychotic drug development. It is unlikely that there will be a «golden shot» for the schizophrenic spectrum disorders in the coming decades, both in terms of diagnostics and treatment. There is a hope that some of the strategies currently being developed (polypharmacy, augmentation), along with new antipsychotic drugs entering the pharmaceutical market, will ultimately become the «shot» that the professional community, patients and their families are looking forward to.

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The role of NMDA receptor antagonists, amantadine and memantine, in schizophrenia treatment: a systematic review

Cited by 3 publications

References 26 publications

SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine

SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine

5-Hydroxytryptophan Reduces Levodopa-Induced Dyskinesia via Regulating AKT/mTOR/S6K and CREB/ΔFosB Signals in a Mouse Model of Parkinson’s Disease

“Golden Shot” in the Treatment and Diagnosis of Schizophrenia: Psychiatrists or Neuroscientists?

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