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1.
Arch. med. res ; 30(2): 125-7, mar.-abr. 1999. ilus
Artigo em Inglês | LILACS | ID: lil-256635

RESUMO

Background. The noncompetitive NMDA antagonists phencyclidine (PCP) and dizocilpine (MK-801) have been considered for use as neuroprotective therapeutic agents, although both produce injury in neurons of cingulate and retrosplenial cortices in rodents. The low-affinity, noncompetitive NMDA antagonist dextrorphan has been considered for use as a neuroprotective therapeutic drug. The aim of the present work was to evaluate the neurotoxicity of dextrorphan. Methods. Sprague-Dawley male rats were used and injected with either saline or dextorphan (30 mg/kg i.p.). The animals were sacrificed 30 min later, and the brain was examined for histopathological changes. Results. After. systemic administration of the drug, hyperchromatic and shrunken nuclei with chromatin condensation and disruption were observed. Also. granular and vacuolated cytoplasm was apparent in pyramidal neurons in the retrosplenial (posterior cingulate) cortex. Status spongious (spongy degeneration) of the neuropil was also detected. Conclusions. Morphological changes are similar to those described previously, which are induced by high-affinity, noncompetitive NMDA antagonists, such as MK-801


Assuntos
Animais , Masculino , Ratos , Dextrorfano/efeitos adversos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/efeitos adversos , Cérebro/efeitos dos fármacos , Ratos Sprague-Dawley
2.
Medicina (B.Aires) ; 56(4): 378-82, 1996. tab, graf
Artigo em Inglês | LILACS | ID: lil-186259

RESUMO

The polymorphic oxidative metabolism of debrisoquine and sparteine were discovered in the seventies by Mahgoub and Eichelbaum. Since then, many other therapeutic substances were added and one of these drugs is dextromethorphan. The object of this investigation was to ascertain the distribution of the oxidative phenotype of dextromethorphan in the Uruguayan population. The drug and its metabolite, dextrorphan, were quantified in the urine of 165 healthy volunteers by a modificacion of an HPLC method by Chen et al. The metabolic ratio was calculated and frequency distribution histograms were drawn. By inspection of the histogram two antimodes can be assigned which determine three sub-populations: on one side the fast extensive metabolizers (n = 30, 18.2 per cent), in the middle the extensive metabolizers (n = 123, 74.5 per cent) and on the other extreme of the histogram the slow metabolizers (n = 12, 7.3 per cent). No other studies have confirmed thus far this trimodal distribution. This research will be continued by genotyping the populations studied in order to confirm these findings and to elucidate the underlying genetic mechanisms of the polymorphism.


Assuntos
Humanos , Masculino , Feminino , Adulto , Dextrometorfano/urina , Dextrorfano/urina , Enzimas/genética , Oxirredutases O-Desmetilantes/metabolismo , Polimorfismo Genético , Fenótipo , Uruguai
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