Galactosylated dopamine enters into the brain, blocks the mesocorticolimbic system and modulates activity and scanning time in Naples high excitability rats

Ruocco, L; Viggiano, D.; Viggiano, Andrea; Abignente, E.; Rimoli, Maria Grazia; Melisi, Daniela; Curcio, Annalisa; Nieddu, Maria; Boatto, Gianpiero; Carboni, Ezio; Carnevale, U.A. Gironi; Sadile, A.G.

doi:10.1016/j.neuroscience.2007.11.021

Cited by 24 publications

(17 citation statements)

References 49 publications

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“…The hydroxy group at the C6 position of glucose holds the greatest potential for drug molecule attachment, while maintaining affinity for the GLUT1 transporter . Attachment of dopamine to the hydroxy groups at the C1 or C3 positions of glucose (but not C6) resulted in only moderate or no binding affinity for the carrier proteins, as observed in studies exploring CNS‐penetrating conjugates . SNAP derivatives, a class of glycosidase‐activated NO donors (Figure ), had been developed to control the site‐specific delivery of NO.…”

Section: Structure–activity Relationshipsmentioning

confidence: 99%

“…The order of their hydrolysis rate was: ester>amide>carbamate>glycoside. Notably, carbamate derivatives 87 , 89 , and 90 were found to be the promising prodrugs according to their good druggability profiles, such as a moderate affinity for GLUT1, adequate stability in plasma, and targeted release of dopamine upon incubation with brain extract …”

Section: Structure–activity Relationshipsmentioning

confidence: 99%

“…[9][10][11][12] Such hexoses are attractive targeting agents for the delivery of drug molecules to destination proteins. Dopamine, [13][14][15][16][17] compounds such as arginine, [18][19][20] and other drugs that act on the brain [21,22] have been conjugated to d-galactose or d-glucose to cross the BBB and enter into the central nervous system( CNS) by specific carrier-mediated transport. More importantly,t hese glycoconjugates have been found to show minimal cardiovascular side effects and better permeability and bioavailability,e mphasizing the importance of the targeting and specificity properties of d-glucose and d-galactose in improving the efficacy of the parent compounds.…”

Section: Targeting Properties Of Mono-and Disaccharides 21 Brain Anmentioning

confidence: 99%

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Application of Mono‐ and Disaccharides in Drug Targeting and Efficacy

Yuan

Chen

et al. 2018

ChemMedChem

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Carbohydrates and their conjugates play important roles in many biological processes including fertilization, differentiation, development, immune response, and infection. Their activities are largely dependent on the properties of terminal mono- or disaccharides. Galactose, mannose, fucose, glucose, sialic acid, etc., are commonly used as powerful scaffolds installed on drug molecules for targeting specific tissues including brain, liver, and cancers, and as epitopes for enhancing the targeting of various vaccines. This review focuses on the influence of their structural variations, including changes in sugar type, substituent groups and their positions, as well as length of linker portion, on the targeting of drugs or their efficacy. Particular attention is paid to the targeting properties of mono- and disaccharides applied in drug design and discovery.

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Section: Structure–activity Relationshipsmentioning

confidence: 99%

Section: Structure–activity Relationshipsmentioning

confidence: 99%

Section: Targeting Properties Of Mono-and Disaccharides 21 Brain Anmentioning

confidence: 99%

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Application of Mono‐ and Disaccharides in Drug Targeting and Efficacy

Yuan

Chen

et al. 2018

ChemMedChem

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“…Intriguingly, these authors reported that whereas DA concentration increases in the neostriatum and prefrontal cortex of NHE, it decreases in NRB rats, after GALDA administration. Such discrepancy has been ascribed to the inadequate functioning of the dopamine membrane transporter (DAT) in NHE rats, induced by GALDA itself; conversely, the decrease in NRB rats has been attributed to the blockade of mesocorticolimbic neurons by D2 autoreceptors and to the normal functioning of DAT [13]. In support of this theory, behavioral data have shown that GALDA administration increases activity in C57 mice [14] which indeed display a low expression of D2 autoreceptors in the mesencephalon [15].…”

Section: Brainmentioning

confidence: 99%

D-Galactose as a Vector for Prodrug Design

Melisi¹,

Curcio²,

Luongo³

et al. 2011

CTMC

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D-galactose is a simple and natural compound that has mainly been exploited in prodrug strategies. Galactosyl prodrugs can be considered a good approach to reach different goals in clinical drug application, especially when traditional drugs are likely to fail therapeutically owing to reasons such as the lack of site specificity, toxicity, and chemical instability. Indeed, of paramount importance is their ability to increase the selectivity of the parent compound, a phenomenon that helps to reduce the incidence of adverse effects, while preserving intact the pharmacodynamic features of the parent drug. Study results have varied according to the type of linkage between the drug and the hydroxyl group exploited. By working with these parameters, researchers have been able not only to generate selective pharmacological targeting of brain, liver, and cancerous cells, but also to improve cellular permeability as well as the pharmacokinetic profile of parent drugs. This review describes the broad spectrum of possibilities for exploiting D-galactose as a vector for prodrug design and the synthetic strategies that allow its realization.

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“…For these properties, ASGP-R has been exploited as a liver-specific targeting marker for gene and drug vehicles [11][12][13]. Galactose was also used as a ligand of hepatocyte-specific targeted agents, including various formulations and prodrugs [14][15][16][17].…”

mentioning

confidence: 99%

Preparation of a novel liver-targeting nanoparticle of norcantharidin derivative and evaluation of its anti-tumour activity

Zhang-Hong

Yiang

Zhang

et al. 2011

Journal of Experimental Nanoscience

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2011) Preparation of a novel livertargeting nanoparticle of norcantharidin derivative and evaluation of its anti-tumour activity, In our study, a novel hepatocyte-targeting norcantharidin (NCTD) derivative lactosyl-norcantharidin (Lac-NCTD) was synthesised using ethanediamine as a truss arm, and lactosyl-norcantharidin nanoparticles (Lac-NCTD-NPs) were obtained by an ionic cross-linkage process with an entrapment efficiency of (80.29 AE 0.56)%. The release of Lac-NCTD-NPs in vitro was then investigated by means of a dialysis method, and its sustained effect was evident. The in vitro anti-tumour activities of Lac-NCTD and Lac-NCTD-NPs were studied by their cytotoxic effects on HepG2, SMMC-7721 and SGC-7901 cells. The results showed that the IC 50 values of Lac-NCTD and Lac-NCTD-NPs cytotoxicity against HepG2 and SMMC-7721 cells were lower compared to NCTD, and the anti-tumour effects could be remarkably inhibited by galactosylated fetal bovine serum (Gal-FBS) as a competitor of the asialoglycoprotein receptor. The cytotoxic effects against SGC-7901 cells were relatively high, even higher than NCTD, and Gal-FBS had no influence on them at all. The amount of Lac-NCTD accumulated in SMMC-7721 cells was assayed by high-performance liquid chromatography, which indicated that Lac-NCTD may be able to permeate the cell membrane in its unchanged form. The anti-tumour activities of Lac-NCTD and Lac-NCTD-NPs in vivo were evaluated in mice bearing an H22 tumour. The results suggested that tumour growth was effectively inhibited by all treatments, including NCTD, Lac-NCTD and Lac-NCTD-NPs, with Lac-NCTD-NPs being the most effective, followed by Lac-NCTD. As a result, Lac-NCTD-NPs may be regarded as liver-targeting agents, which combine both active and passive targeting.

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Galactosylated dopamine enters into the brain, blocks the mesocorticolimbic system and modulates activity and scanning time in Naples high excitability rats

Cited by 24 publications

References 49 publications

Application of Mono‐ and Disaccharides in Drug Targeting and Efficacy

Application of Mono‐ and Disaccharides in Drug Targeting and Efficacy

D-Galactose as a Vector for Prodrug Design

Preparation of a novel liver-targeting nanoparticle of norcantharidin derivative and evaluation of its anti-tumour activity

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