Potential antidepressant effect of amantadine: a review of preclinical studies and clinical trials

Raupp-Barcaro, Inara F.; Vital, Maria A.B.F.; Galduróz, José Carlos Fernandes; Andreatini, Roberto

doi:10.1590/1516-4446-2017-2393

Cited by 28 publications

(21 citation statements)

References 73 publications

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“…The probable cause of agitation and aggression observed in 4 people by Rizzo [ 38 ], which led to the discontinuation of the study, was the high age of people (68 years and older) and just too high of a dose regime of amantadine (300 mg/day) already at the end of the first week of treatment. Amantadine did not cause side effects in most of the previous studies, as in this study [ 7 ].…”

Section: Discussionsupporting

confidence: 66%

“…The antidepressant effect of ketamine was observed already 2 h after drug administration. The presumably clinical effect of amantadine in depression at doses used in patients is mainly related to its action on NMDA receptors [ 7 ]. Since both ketamine and amantadine block NMDA receptors, it can be speculated that it is the blocking of NMDA receptor function, in addition to increasing BDNF concentration, that is associated with the rapid effects of amantadine in bipolar depression.…”

Section: Discussionmentioning

confidence: 99%

“…One of the off-label drugs that have an antidepressant effect is amantadine. The molecular mechanism of amantadine’s antidepressant action is not yet fully understood as the drug exerts its pharmacological effects through diverse brain signaling systems such as dopaminergic, noradrenergic, glutamatergic, and opioid systems [ 7 ]. Several neurochemical scenarios should be considered; however, the effect of amantadine on dopaminergic transmission is relatively well documented.…”

Section: Introductionmentioning

confidence: 99%

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Possibility of a New Indication for Amantadine in the Treatment of Bipolar Depression—Case Series Study

Krzystanek

Pałasz

2020

Pharmaceuticals

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Bipolar disorder is a chronic and remitting mental illness. Antidepressants are not effective in treating acute bipolar depression, and antipsychotic drugs used in the treatment of bipolar depression cause frequent side effects. This situation justifies the search for new drugs as well as the repurposing of drugs used in other indications. In an open and naturalistic serious case study, 4 patients diagnosed with bipolar I disorder, chronically treated with a mood stabilizer, in whom at least two antidepressants were ineffective in the depressive phase, were treated with amantadine. The woman received 100 mg/day and 3 men received the target dose of 200 mg/day. All patients treated with amantadine improved their depressive symptoms after 1 week of treatment. None of them experienced side effects or manic switch. To reduce the risk of a manic switch, the treatment with amantadine was discontinued 2 weeks after the improvement of depressive symptoms, and no recurrence of depressive symptoms was observed. Amantadine may be a further therapeutic option for the treatment of acute bipolar depression. The drug in this indication may act quickly and be well tolerated. Confirmation of the antidepressant efficacy of amantadine in this indication requires replication of the results and conducting clinical trials.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Possibility of a New Indication for Amantadine in the Treatment of Bipolar Depression—Case Series Study

Krzystanek

Pałasz

2020

Pharmaceuticals

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“…Induction of BDNF expression by amantadine in the hippocampus contributed to its antidepressant activity [97]. Moreover, cotreatment of fluoxetine and amantadine significantly induced BDNF expression in the cerebral cortex [98].…”

Section: Amantadinementioning

confidence: 99%

Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

Jin

2020

JCM

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Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase receptor type B (TrkB) are widely distributed in multiple regions of the human brain. Specifically, BDNF/TrkB is highly expressed and activated in the dopaminergic neurons of the substantia nigra and plays a critical role in neurophysiological processes, including neuro-protection and maturation and maintenance of neurons. The activation as well as dysfunction of the BDNF-TrkB pathway are associated with neurodegenerative diseases. The expression of BDNF/TrkB in the substantia nigra is significantly reduced in Parkinson’s Disease (PD) patients. This review summarizes recent progress in the understanding of the cellular and molecular roles of BNDF/TrkB signaling and its isoform, TrkB.T1, in Parkinson’s disease. We have also discussed the effects of current therapies on BDNF/TrkB signaling in Parkinson’s disease patients and the mechanisms underlying the mutation-mediated acquisition of resistance to therapies for Parkinson’s disease.

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“…Adamantan-1ylamine and its derivatives are amines containing adamantyl fragment in the form of three fused cyclohexane rings in a chair conformation (1), and adamantane is the monomer of the diamond lattice (2). The adamantyl group has been found to be an important component in the development of many drug treatments (3). For example, the addition of adamantyl moiety to an active pharmaceutical molecule leads to improvements in an array of therapeutic drugs (4), and adamantan-1-ylamine was the first anti-viral treatment to be developed (5).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Six and Seven-membered Heterocyclic Molecules Containing an Adamantyl Fragment and an X-ray Crystal Structure of (E)-N-(adamantan-1-yl)-1-(3-nitrophenyl)methanimine

Shukkur

2020

Baghdad Sci.J

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Our work included a synthesis of three new imine derivatives-1,3-thiazinan-4-one, 1,3-oxazinan-6-one and 1,3-oxazepin-4,7-dione-which contained an adamantyl fragment. These were produced via the condensation of the Schiff`s base (E)-N-(adamantan-1-yl)-1-(3-aryl)methanimine with 3-mercaptopropanoic acid; 3-chloropropanoic acid; and maleic, citraconic anhydride, respectively. These new imines were prepared via the condensation of adamantan-1-ylamine and 3-nitro-, 3-bromobenzaldehyde in n-BuOH. We obtained a good yield of products. FTIR, 1 H NMR spectroscopy and C.H.N.S analysis were used to diagnostic the products. The molecular structure of (E)-N-(adamantan-1-yl)-1-(3-nitrophenyl)methanimine was confirmed by X-ray crystallography analysis.

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Potential antidepressant effect of amantadine: a review of preclinical studies and clinical trials

Abstract: Amantadine is an interesting candidate as new antidepressant drug for the treatment of depression.

Cited by 28 publications

References 73 publications

Possibility of a New Indication for Amantadine in the Treatment of Bipolar Depression—Case Series Study

Possibility of a New Indication for Amantadine in the Treatment of Bipolar Depression—Case Series Study

Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

Synthesis of Six and Seven-membered Heterocyclic Molecules Containing an Adamantyl Fragment and an X-ray Crystal Structure of (E)-N-(adamantan-1-yl)-1-(3-nitrophenyl)methanimine

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