R-Deprenyl: Pharmacological Spectrum of its Activity

Magyar, K.; Szende, Béla; Jenei, Veronika; Tábi, Tamás; Pálfi, Melinda; Szökő, Éva

doi:10.1007/s11064-010-0238-8

Cited by 23 publications

(9 citation statements)

References 95 publications

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“…Deprenyl-induced enhancement of hypothalamic dopaminergic activity with subsequent secretory suppression of the tumor growth-promoting pituitary hormone PRL may be responsible for our findings, similar to its actions in other mammary tumor models [1,3,19,20]. Inhibition of dopamine uptake into the neuron and increase in the firing-rate of dopaminergic neurons may also be contributory to the enhancing effects of deprenyl on hypothalamic dopaminergic activity similar to its effects in the striatum [12,13]. …”

Section: Discussionsupporting

confidence: 63%

“…L -Deprenyl, a monoamine oxidase inhibitor, has been used as a therapeutic agent in Parkinson's and Alzhei-mer's disease because of its ability to increase the availability of catecholamines, augment the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and growth-factor biosynthesis, and improve neuronal survivability [11,12,13,14]. Previously, we demonstrated that the administration of deprenyl or its metabolite, desmethyldeprenyl, to old male rats reversed the age-related decline in splenic NA innervation and enhanced splenic concanavalin A (Con A)-induced interleukin (IL)-2 production and NK cell activity [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Prevention of Mammary Tumor Development through Neuroimmunomodulation in the Spleen and Lymph Nodes of Old Female Sprague-Dawley Rats by <smlcap>L</smlcap>-Deprenyl

ThyagaRajan¹,

Tran²,

Molinaro³

et al. 2013

Neuroimmunomodulation

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Background: Development of mammary tumors is an age-associated phenomenon that is likely due to deficits in the neuroendocrine-immune interactions. Previously, we demonstrated that L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, can enhance immune responses and restore noradrenergic (NA) innervation in the spleens of rats with carcinogen-induced and spontaneously developing mammary tumors. Objectives: To investigate whether (1) treatment of early middle-aged female rats would prevent the spontaneous development of mammary tumors accompanied by restoration of immunity in the spleen and draining lymph nodes (DLN) and sympathetic NA innervation in the spleen and (2) deprenyl can influence the proliferation of estrogen receptor (ER)-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231 and Hs 578T) human breast cancer cells. Methods: Early middle-aged (8- to 9-month-old) female Sprague-Dawley rats were treated with 0, 1.0 or 2.5 mg of deprenyl/kg body weight (BW) daily i.p. for 12 months. Cells of ER-positive (ER+) and ER-negative (ER-) human breast cancer cell lines were incubated with media or 10^-3 to 10^-8M deprenyl for 1, 2, 4 or 6 days to examine the proliferation of cells. Results: Tumor incidence increased in saline-treated old female rats, while deprenyl treatment significantly reduced the incidence of mammary tumors in these rats. Saline-treated tumor-bearing rats exhibited reduced splenic NA innervation and norepinephrine (NE) content, splenic interleukin (IL)-2 and interferon (IFN)-γ levels and NK cell activity as well as DLN IL-2 and IFN-γ levels compared to young female rats without tumors. In contrast, treatment with 2.5 mg/kg of deprenyl enhanced IL-2 and IFN-γ production in both the spleen and DLN as well as splenic natural killer (NK) cell activity. Deprenyl treatment also increased concanavalin A (Con A)-induced proliferation of T lymphocytes in the DLN. Deprenyl-induced changes in immune responses were accompanied by enhanced NA innervation and NE content in the spleen. In vitro incubation of various concentrations of deprenyl with ER+ human breast cancer cell lines partly inhibited the proliferation of cells, while it had no effect on the ER- breast cancer cells. Conclusions: These results suggest that (1) development of mammary tumors is mediated through the loss of immunity and sympathetic NA nerve fibers accompanied by reduced NE levels in the spleen, (2) the prevention of mammary tumor development by deprenyl may involve the reversal of the tumor-associated decline in sympathetic NA activity and cell-mediated immune responses in the spleen and DLN and (3) the antitumor effects of deprenyl may be partially mediated through ER-dependent intracellular signaling pathways.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Prevention of Mammary Tumor Development through Neuroimmunomodulation in the Spleen and Lymph Nodes of Old Female Sprague-Dawley Rats by <smlcap>L</smlcap>-Deprenyl

ThyagaRajan¹,

Tran²,

Molinaro³

et al. 2013

Neuroimmunomodulation

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“…* p < 0.05 compared to control, # p < 0.05 compared to the LDD group. neurotropic, and immunostimulatory properties (Magyar et al 2010). It is known that deprenyl can upregulate activities of anti-oxidant enzymes such as SOD and CAT in brain dopaminergic regions (Kitani et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Effects of low and high deprenyl dose on antioxidant enzyme activities in the adult rat brain

Lalkovičová

Horváthová²,

Šulla³

et al. 2017

gpb

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We evaluated the effects of low dose deprenyl (LDD, 0.0025 mg/kg per day) and high dose deprenyl (HDD, 0.25 mg/kg per day) treatment of male Wistar rats for 30 days on the activities of SOD and CAT in the cortex, striatum, and hippocampus. Total SOD and MnSOD activities were increased with LDD (p <0.05) in the cortex (0.74 ± 0.03; 0.31 ± 0.02), striatum (0.75 ± 0.02; 0.27 ± 0.03) and CA1 region of the hippocampus (0.75 ± 0.02; 0.29 ± 0.03) compared to the control (0.53 ± 0.02; 0.15 ± 0.02), but reduced (p <0.05) with HDD compared to the LDD group. CAT activity was increased (p <0.05) with LDD in the cortex (27.34 ± 3.11), striatum (22.22 ± 1.85), and hippocampal CA1 region (16.62 ± 2.15) compared to control (10.33 ± 1.01), while a decrease was induced by HDD in the striatum (9.85 ± 1.09) compared to LDD. There was a significant (p <0.05) difference in number of Fluoro Jade B positive CA1 neurons induced by LDD (21.14 ± 2.85%) and HDD (12.61 ± 1.42%), as well as the number of NeuN positive CA1 neurons after LDD (183.35 ± 11.14 cells/mm) and HDD (238.45 ± 14.11 cells/mm (p < 0.05). Deprenyl showed a potential in improving the neurological outcome and reducing the oxidative damage.

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“…The monoamine oxidase inhibitors (MAO-Is) are used clinically as PD therapeutic agents (85). By inhibition of dopamine metabolism, MAO-Is decrease the formation of H 2 O 2 (41,114). Furthermore, MAO-Is also protect against asynuclein toxicity (26).…”

Section: Potential Therapeutic Approachesmentioning

confidence: 99%

Thiol-Redox Signaling, Dopaminergic Cell Death, and Parkinson's Disease

García-García

Zavala-Flores

Rodríguez-Rocha

et al. 2012

Antioxidants & Redox Signaling

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In this review, we summarize major advances in the understanding of the role of thiol-redox signaling in dopaminergic cell death in experimental PD. Future research is still required to clearly understand how integrated thiol-redox signaling regulates the activation of the cell death machinery, and the knowledge generated should open new avenues for the design of novel therapeutic approaches against PD.

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R-Deprenyl: Pharmacological Spectrum of its Activity

Cited by 23 publications

References 95 publications

Prevention of Mammary Tumor Development through Neuroimmunomodulation in the Spleen and Lymph Nodes of Old Female Sprague-Dawley Rats by <smlcap>L</smlcap>-Deprenyl

Prevention of Mammary Tumor Development through Neuroimmunomodulation in the Spleen and Lymph Nodes of Old Female Sprague-Dawley Rats by <smlcap>L</smlcap>-Deprenyl

Effects of low and high deprenyl dose on antioxidant enzyme activities in the adult rat brain

Thiol-Redox Signaling, Dopaminergic Cell Death, and Parkinson's Disease

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