Studies on a new potential dopaminergic agent:<i>in vitro</i>BBB permeability,<i>in vivo</i>behavioural effects and molecular docking evaluation

De, Viviana; Sutera, Flavia Maria; Gentile, Carla; Tutone, Marco; Livrea, Maria Antonia; Almerico, Anna Maria; Cannizzaro, Carla; Giannola, Libero Italo

doi:10.3109/1061186x.2015.1035275

Cited by 10 publications

(6 citation statements)

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“…When these cells achieve confluence, they differentiate into polarized enterocyte‐like monolayers with permeability characteristics similar to those of normal IECs . Therefore, differentiated Caco‐2 cell monolayers represent a well‐characterized intestinal barrier model in vitro and have widely been used in bioavailability studies . On the other hand, differentiated Caco‐2 monolayers submitted to pro‐inflammatory action of LPS or cytokines have been proposed as in in vitro model of intestinal inflammation, which is useful for evaluating potential local effects of food, food components, or per oral drugs …”

Section: Resultsmentioning

confidence: 99%

“…26 Therefore, differentiated Caco-2 cell monolayers represent a well-characterized intestinal barrier model in vitro and have widely been used in bioavailability studies. 27,28 On the other hand, differentiated Caco-2 monolayers submitted to pro-inflammatory action of LPS or cytokines have been proposed as in in vitro model of intestinal inflammation, which is useful for evaluating potential local effects of food, food components, or per oral drugs. 19,25,29 Melatonin, in addition to endogenous synthesis, may be sourced from dietary supplements and melatonin-rich foods.…”

Section: Resultsmentioning

confidence: 99%

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Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

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Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti‐inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL‐1β‐stimulated Caco‐2 cells. Differentiated monolayers of Caco‐2 cells were preincubated with melatonin (1 nmol/L‐50 μmol/L) and then exposed to IL‐1β. After each treatment, different inflammatory mediators, DNA‐breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL‐1β. Anti‐inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL‐6, IL‐8, COX‐2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF‐κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated‐IL‐6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

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“…It is a reliable and fast model for testing potential antidepressant treatments with strong predictive validity 56 . In this study, FST test was done according to Can et al, and De Caro et al, with some modifications 48,57 . The procedures employed in this study were reviewed and approved by the ethics committee of the Faculty of Pharmacy, The British University in Egypt.…”

Section: Assessment Of the Pharmacological Actionmentioning

confidence: 99%

Trazodone Loaded Lipid Core Poly (ε-caprolactone) Nanocapsules: Development, Characterization and in Vivo Antidepressant Effect Evaluation

Elhesaisy

Swidan

2020

Sci Rep

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trazodone Loaded Lipid core poly (ε-caprolactone) nanocapsules: Development, characterization and in Vivo Antidepressant Effect evaluation nahla elhesaisy 1 & Shady Swidan 1,2* Trazodone hydrochloride (TRH) is a lipophilic drug which is used effectively as an antidepressant. Its poor solubility and short half-life represent an obstacle for its successful use. Nanocapsules with biodegradable polymeric shell are successful drug delivery systems for controlling the release of drugs. to enhance the entrapment of lipophilic drugs, oils can be added forming a lipophilic core in which the drug is more soluble. The aim of this study was to enhance the efficacy of TRH and prolong its action by formulating it into lipid core polymeric shell nanocapsules. Nanocapules were prepared using nanoprecipitation technique. All prepared formulations were in nano size range and negatively charged. The TRH entrapment efficiency (EE%) in lipid core nanocapsules was up to 74.8 ± 0.5% when using Labrafac lipophile as a lipid core compared to only 55.7 ± 0.9% in lipid free polymeric nanospheres. Controlled TRH release was achieved for all prepared formulations. Forced swim test results indicated the significant enhancement of antidepressant effect of the selected TRH loaded Labrafac lipophile core nanocapsules formulation compared to control and TRH dispersion in phosphate buffer. It is concluded that lipid core nanocapsules is a promising carrier for the enhancement of TRH efficacy. Depression is one of the most common, chronic and debilitating psychological disorders that may lead eventually to patient suicide 1. It is characterized by many symptoms like feeling hopelessness or inappropriate guilt, low energy, change in sleep, change in appetite and recurrent thoughts of suicide. Its consequences not only affect the patient, but also affect negatively the whole society. The financial consequences of this disease are tremendous and cause an overwhelming burden on the society. This burden is due to the dramatically decrease in productivity and absenteeism in the workplace. Depression mainly occurred due to the deficiency of both serotonin and norepinephrine neurotransmitters in the brain 2. Trazodone hydrochloride (TRH) is one of the most potent drugs used for the treatment of depression (Fig. 1). It is a triazolopyridine derivative with antidepressant effect 3. It is thought that the mechanism of action of TRH is due to its activity at 5-HT1, 5-HT2 serotonergic receptors. It also acts on poorly blocking serotonin reuptake and selectively blocking presynaptic receptors. In addition, TRH blocks alpha-2 adrenoceptors 4. TRH possesses unique properties compared to other antidepressants. TRH causes fewer anticholinergic side effects compared to the tricyclic antidepressant. It also has an activity against anxiety which is concomitant to depressed patients. Several studies showed that at therapeutic doses TRH is less likely to cause cardiotoxicity than imipramine. TRH also does not result in neurologic side effects and seems to be well tolerat...

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“…Giannola et al [ 80 ] have proposed a 2-amino- N -[2-(3,4-dihydroxyphenyl)-ethyl]-3-phenyl-propionamide dopamine prodrug (DA-PHEN) ( Figure 10 ) [ 81 ]. It was synthesized by condensation of dopamine with a neutral amino acid to interact with the BBB endogenous transporters and readily enter the CNS.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, De Caro et al [ 81 ] studied in vitro the ability of DA-PHEN to penetrate the CNS. The team used in their study parallel artificial permeability assay (PAMPA) and Caco-2 models.…”

Section: Introductionmentioning

confidence: 99%

Dopamine and Levodopa Prodrugs for the Treatment of Parkinson’s Disease

et al. 2017

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Background: Parkinson’s disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement therapy, mainly through actual dopamine and its original prodrug l-dopa (LD), faces many challenges such as poor blood brain barrier penetration and decreased response to therapy with time. Methods: The prodrugs described herein are ester, amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, chemical delivery systems and enzyme-models prodrugs designed and made by chemical means, and their bioavailability was studied in animals. Results: A promising ester prodrug for intranasal delivery has been developed. LD methyl ester is currently in Phase III clinical trials. A series of amide prodrugs were synthesized with better stability than ester prodrugs. Both amide and dimeric amide prodrugs offer enhanced blood brain barrier (BBB) penetration and better pharmacokinetics. Attaching LD to sugars has been used to exploit glucose transport mechanisms into the brain. Conclusions: Till now, no DA prodrug has reached the pharmaceutical market, nevertheless, the future of utilizing prodrugs for the treatment of PD seems to be bright. For instance, LD ester prodrugs have demonstrated an adequate intranasal delivery of LD, thus enabling the absorption of therapeutic agents to the brain. Most of the amide, cyclic, peptidyl or chemical delivery systems of DA prodrugs demonstrated enhanced pharmacokinetic properties.

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Studies on a new potential dopaminergic agent:in vitroBBB permeability,in vivobehavioural effects and molecular docking evaluation

Cited by 10 publications

References 54 publications

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Trazodone Loaded Lipid Core Poly (ε-caprolactone) Nanocapsules: Development, Characterization and in Vivo Antidepressant Effect Evaluation

Dopamine and Levodopa Prodrugs for the Treatment of Parkinson’s Disease

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