RESUMO
The effect of enzyme-inhibiting adjuvants on L-DOPA + benserazide-induced contralateral turning in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats was studied. Both the number of turns and the duration of turning were examined. Inhibition of MAO-A with 10 mg/kg Ro 41-1049 increased both parameters; inhibition of COMT with 30 mg/kg Ro 40-7592 had a similar effect. In contrast, inhibition of MAO-B with 10 mg/kg Ro 19-6327 did not change turning behavior. A further potentiation of turning behavior was observed after the combined administration of both the MAO-A and COMT inhibitor. MAO-A inhibition in conjunction with MAO-B inhibition prolonged the duration of L-DOPA-induced turning but had no effect on the number of turns. However, in conjunction with COMT inhibition, 10 mg/kg of the MAO-B inhibitor, Ro 19-6327, significantly affected both the number and duration of turning behavior. An even further potentiation of turning behavior was observed after the combined administration of all three enzyme-inhibitors.
Assuntos
Antiparkinsonianos/farmacologia , Inibidores de Catecol O-Metiltransferase , Inibidores Enzimáticos/farmacologia , Levodopa/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Atividade Motora/efeitos dos fármacos , Animais , Benzofenonas/farmacologia , Masculino , Nitrofenóis , Oxidopamina , Ácidos Picolínicos/farmacologia , Ratos , Rotação , Tiazóis/farmacologia , TolcaponaRESUMO
The last decades have been characterized by impressive research activity in connection with Parkinson's disease (PD). A wealth of new results have enriched our knowledge of the pathophysiology of the disorder and led to new approaches for its therapy. Whereas anticholinergic drugs remained the main, though unsatisfactory, treatment of PD for almost 100 years, the situation has changed since the 1960s. An impetus for this turning-point was given by the finding that the striatum of rats contained a high concentration of dopamine (DA) which until then had been considered to be a mere intermediate of the biosynthesis of noradrenaline and adrenaline, without a physiological role in its own right. Subsequently, the role of dopamine as neurotransmitter and the importance of dopaminergic pathways for the control of extrapyramidal motricity were firmly established. As a consequence, new therapeutic possibilities emerged and the anticholinergic drugs, although still in use, lost their supremacy. The present minireview will be restricted to new treatments which have been developed and introduced since 1960 and to recent pharmacotherapeutic approaches with potential future usefulness.
