Mirtazapine, an antidepressant, antagonizes α(2)-adrenergic autoreceptors and heteroreceptors, which leads to enhanced noradrenergic and serotonergic transmission without inhibiting monoamine transporters. Using a microdialysis technique, we investigated whether co-administration of mirtazapine and a serotonin noradrenaline reuptake inhibitor (SNRI), milnacipran, augments the effects of each drug on the extracellular levels of monoamines by pharmacological synergy. Mirtazapine increased the extracellular levels of noradrenaline and serotonin in the dorsal hippocampus. In contrast, it increased the levels of noradrenaline and dopamine without changing serotonin levels in the prefrontal cortex. Milnacipran increased the levels of all monoamines evaluated in both areas, and the combined treatment with mirtazapine augmented these changes. The combined treatment with idazoxan, an α(2) adrenoceptor antagonist, and milnacipran also increased all monoamine levels in the prefrontal cortex. Ketanserin, a serotonin 5-HT(2A) receptor antagonist, showed no effect in combination with milnacipran, while SB242084, a 5-HT(2C) receptor antagonist, augmented the effects of milnacipran on the levels of serotonin and dopamine in the prefrontal cortex. These results suggest that combined treatment with mirtazapine and milnacipran augments the extracellular levels of noradrenaline, serotonin and dopamine through the blockade of α(2) adrenoceptors without regional specificity, whereas mirtazapine enhances serotonergic transmission in a region-specific manner. 5-HT(2C) receptor antagonism may also partly contribute to the amplification effects of mirtazapine on serotonin and dopamine levels. These neurochemical changes could play a role in reported advantageous clinical effects in patients treated with an SNRI and mirtazapine.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuropharm.2012.01.024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Impact of irradiation conditions on therapy of Lewis lung carcinoma in mice using glucose-ethylenediamine carbon dots.
BMC Cancer
January 2025
Taras Shevchenko National University of Kyiv, 64/13, Volodymyrska Street, Kyiv, 01601, Ukraine.
Background: nowadays, the photoacoustic imaging is in the mainstream of cancer theranostics. In this study the nanoparticles with previously proven photoacoustic imaging properties, i.e.
View Article and Find Full Text PDFRibitol and ribose treatments differentially affect metabolism of muscle tissue in FKRP mutant mice.
Sci Rep
January 2025
McColl-Lockwood Laboratory for Muscular Dystrophy Research, Carolinas Medical Center, Atrium Health Musculoskeletal Institute, 1000 Blythe Blvd. , Charlotte, NC, 28231, USA.
Dystroglycanopathy is characterized by reduced or lack of matriglycan, a cellular receptor for laminin as well as other extracellular matrix proteins. Recent studies have delineated the glycan chain structure of the matriglycan and the pathway with key components identified. FKRP functions as ribitol-5-phosphate transferase with CDP-ribitol as the substrate for the extension of the glycan chain.
View Article and Find Full Text PDFMicroglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson's disease model triggered by α-synuclein overexpression.
NPJ Parkinsons Dis
January 2025
Department of Neurobiology, Center of Parkinson Disease Beijing Institute for Brain Disorders, Beijing Key Laboratory on Parkinson Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, 100069, China.
Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to the neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss in mice via rAAV-hSYN injection to cause the neuronal expression of α-synuclein, which produced neuroinflammation and behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior to rAAV-hSYN injection, maintaining it for 8 weeks to eliminate microglia.
View Article and Find Full Text PDFLong-Term Effect of Tafamidis on Clinical Parameters and Prognostic Predictors in Patients With Transthyretin Amyloid Cardiomyopathy.
Circ J
January 2025
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University.
Background: Accurate prediction of prognosis in transthyretin amyloid cardiomyopathy (ATTR-CM) is crucial for optimal treatment selection, including tafamidis, the only approved therapy for ATTR-CM. Although tafamidis has been proven to improve prognosis, the long-term serial changes in comprehensive parameters related to ATTR-CM, including cardiac biomarkers and imaging parameters, under tafamidis remain unknown.
Methods And Results: In this study, we used Cox regression analysis on data from 258 consecutive patients diagnosed with ATTR-CM at Kumamoto University to determine prognostic factors.
In silico analysis and gene expression patterns of lignin peroxidase isozymes in Phanerochaete chrysosporium.
Int J Biol Macromol
January 2025
Plant Genetic Engineering Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641046, Tamil Nadu, India. Electronic address:
Phanerochaete chrysosporium (Pc), is a prominent lignin-degrading fungus which serves as an important source for lignin-degrading enzymes (LDEs). The present study was focused on a detailed in silico analysis and gene expression patterns of lignin peroxidases (PcLiPs), which is a significant class of LDEs. In spite of extensive research on P.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!