Catechol‐O‐methyltransferase Inhibition in Erythrocytes and Liver by BIA 3‐202 (1‐[3,4‐dibydroxy‐5‐nitrophenyl]‐2‐phenyl‐ethanone)

Abstract: The present study evaluated the relationship between the degree of catechol‐O‐methyltransferase (COMT) inhibition in erythrocytes and liver by BIA 3‐202 (1‐3,4‐dihydroxy‐5‐nitrophenyl]‐2‐phenyl‐ethanone) and determined its effects upon the O‐methylation of L‐DOPA in rats orally treated with L‐DOPA plus benserazide. The soluble form of COMT (S‐COMT) in erythrocytes was endowed with the same affinity as liver S‐COMT for the substrate adrenaline. BIA 3‐202 inhibited erythrocytes and liver S‐COMT with ED50's of 1.9 (0.7, 3.1) and 1.9 (0.5, 3.2) (95% confidence limits) mg kg^?1, respectively. BIA 3‐202 reduced the L‐DOPA‐induced rise of 3‐O‐methyl‐L‐DOPA in the peripheral circulation, striatal dialysate levels and striatum, and increased dopamine striatal levels. In BIA 3‐202‐treated rats the increase in L‐DOPA in peripheral blood and striatal dialysates was significantly greater than in vehicle‐treated rats. It is concluded that S‐COMT activity in erythrocytes may provide important information on the pharmacodynamic profile of COMT inhibitors. The novel COMT inhibitor BIA 3‐202 is a potent COMT inhibitor that enhances the availability of L‐DOPA to the brain by reducing its O‐methylation, which may prove beneficial in patients with Parkinson's disease treated with L‐DOPA.