Evidence map›Paper›PMID 41625183›Full record

ArticleNeurology research international2026

Synergistic Effects of Levodopa, Benserazide, and Nortriptyline on Behavioral Impairments and Brain Pathology in an Experimental Rat Model of Parkinson's Disease.

Maryam Ezzedin, Sam Zarbakhsh, Houman Parsaei, Ali Ghanbari, Abbas Ali Vafaei, Zohre Mohsenvand, Seyed Ali Seyedinia, Parnia Tarahomi, Manouchehr Safari

Abstract read
In one paragraph

Article in Neurology research international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Maryam EzzedinNervous System Stem Cells Research Center, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.
Sam ZarbakhshNervous System Stem Cells Research Center, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.
Houman ParsaeiNervous System Stem Cells Research Center, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.
Ali GhanbariResearch Center of Physiology, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.ORCID https://orcid.org/0000-0002-7568-3681
Abbas Ali VafaeiResearch Center of Physiology, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.
Zohre MohsenvandNervous System Stem Cells Research Center, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.
Seyed Ali SeyediniaNervous System Stem Cells Research Center, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.
Parnia TarahomiNervous System Stem Cells Research Center, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.
Manouchehr SafariNervous System Stem Cells Research Center, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran, semums.ac.ir.ORCID https://orcid.org/0000-0001-6975-7747

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). In addition to postural instability, rigidity, tremor, and bradykinesia, patients will experience depression and/or anxiety at any time during PD. Nortriptyline, as a dual reuptake inhibitor of norepinephrine and serotonin, inhibits alpha-synuclein aggregation and may play an important role in improving the pathological effects of PD. Objective: This study investigated the effects of nortriptyline combined with L-DOPA and benserazide on behavioral, histological, and biochemical changes in a rat model of PD. Methods. Forty-nine rats were randomly assigned to seven groups. Except for the control and sham groups, five other groups underwent stereotactic surgery for the 6-OHDA lesion. We performed a tail suspension swing test and an apomorphine-induced rotation test after 1 week to confirm the PD model. After gradual treatment with three doses (5, 10, and 20 mg/kg) of nortriptyline combined with L-DOPA and benserazide, the elevated plus-maze test and open field test were performed to determine motor activities, anxiety, and depression. Tissue alterations were evaluated through Nissl staining, tyrosine hydroxylase immunohistochemistry, and Golgi-Cox staining, whereas oxidative stress levels were determined by analyzing malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (TAC) markers. Results: Our results demonstrate that 10 mg/kg of nortriptyline in combination with L-DOPA and benserazide significantly improved motor activity and reduced the anxiety- and depression-like behaviors of PD. Histological findings also suggested a protective effect of nortriptyline on dopaminergic neurons in the SNpc. Furthermore, the findings from the antioxidant evaluation and the structure of CA1 hippocampal neurons indicated that a dosage of 10 mg/kg of nortriptyline might provide the greatest supportive benefit. Conclusion: Nortriptyline at 10 mg/kg offers a promising adjunctive therapy for alleviating both motor and nonmotor symptoms of PD. However, higher doses may induce anxiogenic effects, suggesting the need for careful dose optimization.

Indexed as

anxietybenserazidelevodopamotor activitynortriptylineParkinson’s disease

Identifiers

PMID41625183
PMCPMC12852062

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.