RESUMO
After evaluation of activity in an open field, norepinephrine (NE), serotonin (5HT), 5-hydroxyindolacetic acid (5HIAA), homovanillic acid (HVA), and choline acetyltransferase (CAT) were investigated in cortex of 26-month-old rats poisoned with methylazoxymethanol (MAM) as compared to control rats of the same age. NE and 5HT concentrations showed a marked increase, but levels were normal when expressed as total content, just as in MAM-exposed young adults. Concentrations of 5HIAA were also increased but to a lesser extent than 5 HT. Aged MAM rats did not show any modification of spontaneous activity although hyperactivity is characteristic of young adults exposed to MAM. Together with this behavioral observation, a significant decrease in total HVA content was measured. Because HVA levels seem correlated with activity in MAM-exposed rats, we speculate that the behavioral abnormality recovers in old age. Total CAT activity was also reduced. These results indicate that the neurochemical pattern of young adult MAM-poisoned rats is conserved in aged rats except for some changes in the dopaminergic and cholinergic systems.
Assuntos
Envelhecimento/fisiologia , Acetato de Metilazoximetanol/farmacologia , Envelhecimento/metabolismo , Animais , Monoaminas Biogênicas/metabolismo , Peso Corporal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Colina O-Acetiltransferase/metabolismo , DNA/biossíntese , Feminino , Proteínas do Tecido Nervoso/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Ratos , Ratos Endogâmicos , Sinapses/efeitos dos fármacos , Sinapses/metabolismoRESUMO
A new nitrendipine derivative [ethyl-2-(1-piperidino)ethyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)- 3,5-pyridine dicarboxylate hydrochloride;1] was assayed in plasma by high-performance liquid chromatography. After deproteinization and extraction, 1 and nitrendipine, as the external standard, were separated by ion-pair chromatography and measured by UV detection (254 nm). The method is rapid and specific: the limit of sensitivity of the assay was 5 ng/mL and the concentration range was linear between 5 and 2000 ng/mL. In vitro studies showed that, in contrast to nifedipine and nicardipine, 1 and nitrendipine were stable when exposed to light for at least 4 h. Pharmacokinetic parameters obtained in three beagle dogs after oral and intravenous administration are reported. Comparison with a nicardipine pharmacokinetic study showed similar results for the distribution and elimination characteristics of these two drugs.