CB1 receptors and endocannabinoids are integrated components of neuronal networks controlling different organism’s functions, such as appetite and food intake in the hypothalamus. A series of Rimonabant/Fubinaca hybrids have been synthesized in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied in cannabinoid receptor binding assay and functional receptor assay in vitro, the most active among them as agonist (LONI 11) and antagonist (LONI 4) were tested in vivo to evaluate their ability to stimulate or suppress the feeding behavior after i.p. administration. For LONI 11 formalin test and tail flick tests after s.c. and i.c.v. routes respectively, were also performed in vivo with the aim to investigate the antinociceptive effect at the central or peripheral level. In the Zymosan-induced edema and hyperalgesia, LONI 11 reduced the % paw volume increase and % paw latency after s.c. administration, also suggesting a potential anti-inflammatory activity at the periphery. Keywords. Cannabinoid receptor, Rimonabant, food intake, anorexant agent, edema.

Discovery of orexant and anorexant agents with indazole scaffold endowed with peripheral antiedema activity / Dimmito, Marilisa P.; Stefanucci, Azzurra; Pieretti, Stefano; Minosi, Paola; Dvorácskó, Szabolcs; Tömböly, Csaba; Zengin, Gokhan; Mollica, Adriano. - In: BIOMOLECULES. - ISSN 2218-273X. - 9:9(2019). [10.3390/biom9090492]

Discovery of orexant and anorexant agents with indazole scaffold endowed with peripheral antiedema activity

Stefano Pieretti;Paola Minosi;Adriano Mollica
2019

Abstract

CB1 receptors and endocannabinoids are integrated components of neuronal networks controlling different organism’s functions, such as appetite and food intake in the hypothalamus. A series of Rimonabant/Fubinaca hybrids have been synthesized in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied in cannabinoid receptor binding assay and functional receptor assay in vitro, the most active among them as agonist (LONI 11) and antagonist (LONI 4) were tested in vivo to evaluate their ability to stimulate or suppress the feeding behavior after i.p. administration. For LONI 11 formalin test and tail flick tests after s.c. and i.c.v. routes respectively, were also performed in vivo with the aim to investigate the antinociceptive effect at the central or peripheral level. In the Zymosan-induced edema and hyperalgesia, LONI 11 reduced the % paw volume increase and % paw latency after s.c. administration, also suggesting a potential anti-inflammatory activity at the periphery. Keywords. Cannabinoid receptor, Rimonabant, food intake, anorexant agent, edema.
2019
cannabinoid receptors; rimonabant; food intake; anorexant agent; edema
01 Pubblicazione su rivista::01a Articolo in rivista
Discovery of orexant and anorexant agents with indazole scaffold endowed with peripheral antiedema activity / Dimmito, Marilisa P.; Stefanucci, Azzurra; Pieretti, Stefano; Minosi, Paola; Dvorácskó, Szabolcs; Tömböly, Csaba; Zengin, Gokhan; Mollica, Adriano. - In: BIOMOLECULES. - ISSN 2218-273X. - 9:9(2019). [10.3390/biom9090492]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1313507
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