RESUMO
A series of epibatidine analogs and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Also some of their simplified analogs bearing a 3-piperidine moiety are reported. Their receptor binding profiles (5-HT1A, 5-HT1B, M1, M2, neuronal nicotinic receptor) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Some of the compounds, especially those containing an 8-azabicyclo[3.2.1]oct-2-ene moiety possess high afinity for the nicotinic cholinergic receptor. The most analgesically active compounds are also highly toxic. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of compounds 1-9 were compared with that of epibatidine.
Assuntos
Analgésicos não Narcóticos/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Piridinas/síntese química , Analgésicos não Narcóticos/metabolismo , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Masculino , Camundongos , Piridinas/metabolismo , Ratos , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Receptores de Serotonina/metabolismoRESUMO
A series of epibatidine analogues and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Some of the compounds, especially those containing 8-azabicyclo[3.2.1]oct-2-ene moiety show high affinity for the nicotinic cholinergic receptor.
Assuntos
Analgésicos não Narcóticos/síntese química , Analgésicos não Narcóticos/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Agonistas Nicotínicos/síntese química , Agonistas Nicotínicos/metabolismo , Piridinas/síntese química , Piridinas/metabolismo , Analgésicos não Narcóticos/farmacologia , Animais , Ligação Competitiva , Encéfalo/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Átrios do Coração/metabolismo , Concentração Inibidora 50 , Isomerismo , Cinética , Agonistas Nicotínicos/farmacologia , Piridinas/farmacologia , Ensaio Radioligante , Ratos , Receptor Muscarínico M1 , Receptor Muscarínico M2 , Receptor 5-HT1B de Serotonina , Receptores Muscarínicos/metabolismo , Receptores de Serotonina/metabolismo , Receptores 5-HT1 de SerotoninaRESUMO
Kidneys from broiler chickens at slaughter (6 to 7 weeks of age and mixed sex) were collected by U.S. Department of Agriculture personnel. Forty kidneys were collected from grossly normal birds with grossly normal kidneys (Group D). Grossly swollen kidneys were collected from birds that were otherwise grossly normal (Group A), that had gross lesions of Marek's disease (Group B), or that had gross lesions of squamous cell carcinoma (Group C). These kidneys were fixed in Carson's 10% buffered formalin, embedded in plastic, sectioned at 2 microns, and then stained with periodic acid-Schiff-hematoxylin for glomerular cell counting. Tissue was also processed for electron microscopy from six Group D birds and from six birds total from Groups A, B, and C that had the most severe histologic glomerular lesions. Glomerular tuft cell counts and visceral epithelial cell counts were performed by light microscopy at a magnification of 100x (oil immersion). Total tuft cell counts of all abnormal groups (A, B, and C) were significantly higher (P < 0.05) than those of Group D. Reptilian glomerular tuft cell counts for all abnormal groups were significantly higher (P < 0.05) than the reptilian glomerular tuft counts for Group D. Mammalian glomerular tuft cell counts for Groups A and B were significantly higher than those of the control group (Group D). Electron microscopic examination of the glomeruli from selected birds revealed no dense deposits in the basement membrane and no effacement of epithelial podocyte foot processes. No essential ultrastructural differences were noted between the control group and the abnormal groups.