Objectives: 

In the present study, we hypothesized that administration of a combination of a monoamine oxidase (MAO) inhibitor (isatin) and a catechol-O-methyltransferase (COMT) inhibitor (tropolone) could produce significant increases in the dopamine (DA) levels accompanied by a decrease of its metabolites. To this, we have evaluated the effects of isatin combined with tropolone on in vivo release of DA and its metabolites in the striatum of awake and free moving rats.

Materials: 

Isatin (10 mM) and tropolone (1 mM) have been administrated during a period of 1 hour, directly in striatum of female Sprague-Dawley adult rats (4-7/group) through a microdialysis probe. In order to determine the effect of coadministration of isatin with tropolone, isatin (10 mM) was diluted with tropolone (1 mM) in the same medium. DA and its metabolites (DOPAC and HVA) levels, sampled by microdialysis, have been measured by HPLC with electrochemical detection. The statistical analysis was made by ANOVA and Student-Newman-Kleus multiple range test. Significant differences: P<0.05; P<0.01 and P<0.001.

Results: 

Administration of isatin increased striatal DA levels to 1449.3±272.8%, and significantly decreased DOPAC levels to 82.6±10.5%, with respect to basal. Infusion of isatin did not produce significant changes in the HVA levels. Intrastriatal perfusion of tropolone increased DA and DOPAC to 240.9±63.3% and 211.8±21.8% respectively, and had no significant effect on HVA. Administration of isatin combined with tropolone increased DA to 3038±857% and decreased significantly DOPAC and HVA to 77.5±14.3% and 75.1±11.7%, respectively.

Conclusions: 

When isatin was coinfused into striatum with tropolone, the DA release increased over 30 times, showing an additive effect between isatin and tropolone. Coadministration of isatin with tropolone decreased significantly both DOPAC and HVA levels.

These results support the approach that the combination of MAO and COMT inhibitors may be useful in the Parkinson's disease treatment.