RESUMO
A series of 2-substituted- and 2,3-disubstituted-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-1H- pyrroles was synthesized and found to be active in the rat adjuvant arthritis model of inflammation. The most active compounds were the 2-halo derivatives in the order of chloro > bromo > iodo. The same pattern of activity was observed for the 2,3-dihalopyrroles. Quantitative structure-activity relationship studies suggested that the activity could be correlated with the molar refractivity and the inductive field effect of the 2-substituent and the lipophilicity of the 3-substituent.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Pirróis/síntese química , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/toxicidade , Artrite Experimental/tratamento farmacológico , Modelos Animais de Doenças , Tolerância a Medicamentos , Masculino , Pirróis/farmacocinética , Pirróis/uso terapêutico , Pirróis/toxicidade , Ratos , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
A neurologic deficit characterized by hypokinesia, postural flexion, and to a lesser extent, rigidity, tremor and myoclonus, has been observed in cynomolgus monkeys following administration of 1-methyl-4-(1-methylpyrrol-2-yl)-4-piperidinol (MMPP), a novel 4-substituted piperidine. The syndrome, similar to that described for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), developed within 3-7 days after oral or i.v. dosing, and was accompanied by lesions in the substantia nigra. The behavioral syndrome was seen to a lesser extent in dogs but not in rats. MMPP contains a hydroxyl group on the 4-position of the pyridine ring; the corresponding dehydration product was inactive.
Assuntos
Neurotoxinas/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Peróxidos/toxicidade , Ácidos Ftálicos , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Feminino , Macaca fascicularis , Masculino , Neurotoxinas/administração & dosagem , Doença de Parkinson Secundária/patologia , Doença de Parkinson Secundária/fisiopatologia , Peróxidos/administração & dosagem , Ratos , Ratos Endogâmicos , Substância Negra/efeitos dos fármacosRESUMO
Deaths during dental and oral surgical procedures may lead to litigation alleging malpractice. For this reason, and because of their sudden and unexpected nature, they often come to the attention of forensic pathologists. We review the clinical and anatomic findings of a 3-year-old boy who expired following an oral surgical procedure in the temporomandibular region. During the operation, perforation of the base of the skull occurred causing laceration of a branch of the middle meningeal artery and fatal subdural and epidural bleeding.