RESUMEN
The synthesis of the enantiomers of bupropion, (rac)-2-tert-butylamino-3'-chloropropiophenone 1 (Wellbutrin) is described. The enantiomers were compared with the racemate in both the tetrabenazine-induced sedation model and the inhibition of uptake of biogenic amine assay. No significant differences were found in their potencies to reverse tetrabenazine-induced sedation in mice or in their IC50 values as inhibitors of biogenic amine uptake into nerve endings obtained from mouse brain.
Asunto(s)
Aminas Biogénicas/metabolismo , Bupropión/síntesis química , Bupropión/farmacología , Animales , Bupropión/química , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Indicadores y Reactivos , Masculino , Ratones , Ratones Endogámicos , Norepinefrina/metabolismo , Serotonina/metabolismo , Estereoisomerismo , Relación Estructura-Actividad , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo , Tetrabenazina/antagonistas & inhibidores , Tetrabenazina/farmacologíaRESUMEN
A selected group of alkoxy- and halogen-substituted 5-benzylidino- and 5-benzylhydantoins was prepared and screened for anticonvulsant activity as measured by the ability of the compound to prevent maximal electroshock and metrazol-induced threshold clonic seizures in rats. The structure-activity studies revealed 5-[3-(trifluoromethyl)benzyl]hydantoin (14) to be the most potent member of the series.