RESUMO
Neuropeptide Y (NPY) induces analgesic-like effects after central administration across diverse pain models in rodents. In spinal pain models, previous studies indicate a prominent role for Y(1) receptors at mediating this effect of NPY. In supraspinal pain models like the hot plate test, the NPY receptors involved have not been thoroughly explored. By intracerebroventricular (i.c.v.) administration of selective NPY receptor ligands, the possible involvement of Y(5) receptors in analgesic-like mechanisms was investigated using the hot plate test in rats. Both NPY and selective Y(5) agonists induced analgesic-like effects as revealed by prolonged hot plate latencies. Further consistent with a role for Y(5) receptors, pretreatment with a selective Y(5) receptor antagonist blocked the Y(5) agonist-induced analgesic-like effect. The present study indicates involvement of Y(5) receptors probably at the supraspinal level in mediation of NPY agonist-induced analgesic-like effects in the hot plate test.
Assuntos
Analgésicos/farmacologia , Temperatura Alta , Neuropeptídeo Y/farmacologia , Dor/prevenção & controle , Receptores de Neuropeptídeo Y/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Injeções Intraventriculares , Neuropeptídeo Y/administração & dosagem , Dor/fisiopatologia , Fragmentos de Peptídeos/farmacologia , RatosRESUMO
The known KDR inhibitor SU5416 and several analogues of the indolin-2-one family were surprisingly found to be highly efficacious in the EAE model, an established model for multiple sclerosis. The high in vivo effect could be correlated to in vitro inhibition of the pro-inflammatory cytokine IL-2. Activity following po administration was obtained with several analogues and via the use of prodrugs.
Assuntos
Encefalomielite Autoimune Experimental/metabolismo , Indóis/síntese química , Esclerose Múltipla/metabolismo , Animais , Encefalomielite Autoimune Experimental/tratamento farmacológico , Técnicas In Vitro , Indóis/química , Indóis/farmacologia , Interleucina-2/antagonistas & inibidores , Interleucina-2/biossíntese , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Camundongos , Esclerose Múltipla/tratamento farmacológico , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Resin-bound 1-hydroxyimidazole, obtained by alkylation of the sodium salt of 1-hydroxyimidazole with chloromethyl polystyrene, was lithiated at C-2 with n-butyllithium. Subsequent treatment with carbon, halogen, or sulfur electrophiles followed by detachment from the solid support by heating with trifluoracetic acid at 100 degrees C for 20 h gave 2-substituted 1-hydroxyimidazoles in 52-93% yields.