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dc.contributor.authorCumella Montánchez, José María-
dc.contributor.authorHernández-Folgado, Laura-
dc.contributor.authorGómez-Cañas, M.-
dc.contributor.authorGirón, Rocío-
dc.contributor.authorSánchez, E.-
dc.contributor.authorMorales, Paula-
dc.contributor.authorHurst, D. P.-
dc.contributor.authorGómez-Cañas, M.-
dc.contributor.authorGómez-Ruiz, M.-
dc.contributor.authorPinto, Diana C. G. A.-
dc.contributor.authorGoya, Pilar-
dc.contributor.authorReggio, P. H.-
dc.contributor.authorMartín, M. Isabel-
dc.contributor.authorFernández-Ruiz, Javier-
dc.contributor.authorSilva, Artur M. S.-
dc.contributor.authorJagerovic, Nadine-
dc.date.accessioned2012-12-19T12:32:15Z-
dc.date.available2012-12-19T12:32:15Z-
dc.date.issued2012-
dc.identifierdoi: 10.1002/cmdc.201100568-
dc.identifierissn: 1860-7179-
dc.identifiere-issn: 1860-7187-
dc.identifier.citationChemMedChem 7: 452- 463 (2012)-
dc.identifier.urihttp://hdl.handle.net/10261/63297-
dc.description.abstractThe unwanted psychoactive effects of cannabinoid receptor agonists have limited their development as medicines. These CB 1-mediated side effects are due to the fact that CB 1 receptors are largely expressed in the central nervous system (CNS). As it is known that CB 1 receptors are also located peripherally, there is growing interest in targeting cannabinoid receptors located outside the brain. A library of chromenopyrazoles designed analogously to the classical cannabinoid cannabinol were synthesized, characterized, and tested for cannabinoid activity. Radioligand binding assays were used to determine their affinities at CB 1 and CB 2 receptors. Structural features required for CB 1/CB 2 affinity and selectivity were explored by molecular modeling. Some compounds in the chromenopyrazole series were observed to be selective CB 1 ligands. These modeling studies suggest that full CB 1 selectivity over CB 2 can be explained by the presence of a pyrazole ring in the structure. The functional activities of selected chromenopyrazoles were evaluated in isolated tissues. Invivo behavioral tests were then carried out on the most effective CB 1 cannabinoid agonist, 13a. Chromenopyrazole 13a did not induce modifications in any of the tested parameters on the mouse cannabinoid tetrad, thus discounting CNS-mediated effects. This lack of agonistic activity in the CNS suggests that this compound does not readily cross the blood-brain barrier. Moreover, 13a can induce antinociception in a rat peripheral model of orofacial pain. Taking into account the negative results obtained with the hot-plate test, the antinociception induced by 13a in the orofacial test could be mediated through peripheral mechanisms. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.-
dc.language.isoeng-
dc.publisherWiley-VCH-
dc.rightsclosedAccess-
dc.titleChromenopyrazoles: Non-psychoactive and Selective CB 1 Cannabinoid Agonists with Peripheral Antinociceptive Properties-
dc.typeartículo-
dc.identifier.doi10.1002/cmdc.201100568-
dc.date.updated2012-12-19T12:32:16Z-
dc.description.versionPeer Reviewed-
Appears in Collections:(IQM) Artículos
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